Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is cruci...Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.展开更多
Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present...Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present the development and evaluation of a novel glycosylase-based cytosine base editor(gCBE)for efficient C-to-G editing in rice.Unlike traditional cytosine base editors,which rely on cytosine deamination,gCBE directly excises cytosine to generate an apurinic/apyrimidinic(AP)site,thus circumventing the deamination step and reducing the production of C-to-T byproducts.We constructed several gCBE variants,including N-gCBE,M-gCBE,and C-gCBE,by fusing engineered human UDG2(UNG*)to SpCas9 nickase(nSpCas9,D10A)and tested their editing efficiency and specificity in rice.Our results demonstrate that M-gCBE achieved efficient C-to-G editing(6.3%to 37.5%)similar to OsCGBE(9.4%to 28.1%)at most targets,though with site-dependent variations.Notably,gCBE tools showed a marked reduction in C-to-T byproducts,with average C-to-T mutation rates of 12.5%for N-gCBE and 16.7%for M-gCBE,compared to 53.1%for OsCGBE.Notably,both N-gCBE and M-gCBE were capable of generating homozygous C-to-G mutations in the T_(0)generation,a key advantage over OsCGBE,which predominantly generated C-to-T mutations.Off-target analysis revealed minimal off-target effects with M-gCBE,highlighting its potential for high-precision genome editing.These findings suggest that gCBE tools,particularly M-gCBE,are highly efficient and precise,providing an advanced solution for C-to-G editing in plants and offering promising applications for crop improvement.展开更多
The advent of genome editing technologies,particularly CRISPR/Cas9,has significantly advanced the generation of legume mutants for reverse genetic studies and understanding the mechanics of the rhizobial symbiosis.The...The advent of genome editing technologies,particularly CRISPR/Cas9,has significantly advanced the generation of legume mutants for reverse genetic studies and understanding the mechanics of the rhizobial symbiosis.The legume–rhizobia symbiosis is crucial for sustainable agriculture,enhancing nitrogen fixation and improving soil fertility.Numerous genes with a symbiosis-specific expression have been identified,sometimes exclusively expressed in cells forming infection threads or in nitrogen-fixing nodule cells.Typically,mutations in these genes do not affect plant growth.However,in some instances,germline homozygous mutations can be lethal or result in complex pleiotropic phenotypes that are challenging to interpret.To address this issue,a rhizobia-inducible and cell-type-specific CRISPR/Cas9 strategy was developed to knock-out genes in specific legume transgenic root tissues.In this review,we discuss recent advancements in legume genome editing,highlighting the cell-type-specific CRISPR system and its crucial applications in symbiotic nitrogen fixation and beyond.展开更多
Incorporating a low density of ester units into the backbone of polyethylene materials enhances their sustainability and recyclability while maintaining the main material properties of polyethylenes.Here we report a n...Incorporating a low density of ester units into the backbone of polyethylene materials enhances their sustainability and recyclability while maintaining the main material properties of polyethylenes.Here we report a new way to access degradable polyethylene materials with a low content of in-chain ester units via mechanochemical backbone editing.Initially,ester groups are incorporated as side groups through catalytic copolymerization of ethylene with a cyclobutene-fused lactone monomer(CBL),yielding polyethylene materials with high molecular weights and adjustable thermomechanical properties.Subsequent solid-state ball-milling treatment selectively introduces side-chain ester groups into the main chain of the polyethylene materials via force-induced cycloreversion of the cyclobutane units.Under acidic conditions,hydrolysis of the resultant polyethylene materials with in-chain ester units facilitates further degradation into oligomers.展开更多
The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical...The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical limitations persist in current computational tools for quantifying editing efficiency-particularly concerning data processing capabilities,analytical throughput,and operational flexibility.This research presents SuperDecode,a novel computational framework designed to address these methodological constraints.The SuperDecode offers key advantages,including local processing capabilities,large-size sequencing files,batch-processing,and diversified operational functions.展开更多
Precise chromosome engineering has traditionally relied on the Cre-Lox recombination system-an approach in which the enzyme Cre functions like molecular scissors,cutting and rejoining DNA at specific“Lox”sites to ad...Precise chromosome engineering has traditionally relied on the Cre-Lox recombination system-an approach in which the enzyme Cre functions like molecular scissors,cutting and rejoining DNA at specific“Lox”sites to add,remove,or flip genomic DNA segments inside living cells.展开更多
Genome editing in plants is a powerful strategy that can substantially advance functional genomics research,facilitating the discovery,enhancement,and development of novel traits with significant agricultural implicat...Genome editing in plants is a powerful strategy that can substantially advance functional genomics research,facilitating the discovery,enhancement,and development of novel traits with significant agricultural implications.Various methodologies,such as zinc finger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),and CRISPR/Cas systems,have been developed for this purpose.展开更多
Mutations in the Rhodopsin(RHO)gene are the main cause of autosomal dominant retinitis pigmentosa(adRP),84%of which are pathogenic gain-of-function point mutations.Treatment strategies for adRP typically involve silen...Mutations in the Rhodopsin(RHO)gene are the main cause of autosomal dominant retinitis pigmentosa(adRP),84%of which are pathogenic gain-of-function point mutations.Treatment strategies for adRP typically involve silencing or ablating the pathogenic allele,while normal RHO protein replacement has no meaningful therapeutic benefit.Here,we present an adenine base editor(ABE)-mediated therapeutic approach for adRP caused by RHO point mutations in vivo.The correctable pathogenic mutations are screened and verified,including T17M,Q344ter,and P347L.Two adRP animal models are created carrying the class 1(Q344ter)and class 2(T17M)mutations,and dual AAV-delivered ABE can effectively repair both mutations in vivo.The early intervention of ABE8e efficiently corrects the Q344ter mutation that causes a severe form of adRP,delays photoreceptor death,and restores retinal function and visual behavior.These results suggest that ABE is a promising alternative to treat RHO mutation-associated adRP.Our work provides an effective spacer-mediated point mutation correction therapy for dominantly inherited ocular disorders.展开更多
Clustered regularly interspaced short palindromic repeat sequences(CRISPR)and their accompanying proteins(Cas),commonly presenting in bacteria and archaea,make up the CRISPR/Cas system.As one of the funda-mental sourc...Clustered regularly interspaced short palindromic repeat sequences(CRISPR)and their accompanying proteins(Cas),commonly presenting in bacteria and archaea,make up the CRISPR/Cas system.As one of the funda-mental sources of nutrition for humans,edible crops play a crucial role in ensuring global food security.CRISPR/Cas9 gene editing has been applied to improve many crop traits,such as increasing nitrogen utilization efficiency,creating male sterile germplasm,and regulating tiller and spikelet formation.This paper provides a comprehensive overview of the use of CRISPR/Cas gene editing technology in crop genomes,covering the targeted genes,the types of editing that take place,the mechanism of action.Finally,we also discussed the efficiency of gene editing and pointed the future direction on how to speed up crop molecular breeding,increase breeding effectiveness,and produce more new crop varieties with high qualities.展开更多
As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant chal...As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.展开更多
The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional ...The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional regenerative medicine and tissue engineering strategies have created specialized tissues using progenitor cells and various biological stimuli.To date,there are many US Food and Drug Administration(FDA)-approved regenerative medicine therapies,such as those for wound healing and orthopedic injuries.Nonetheless,these therapies face challenges,including off-target effects,a lack of precision,and failure to target the disease or injury at its origin.In search of novel,precise,and efficient alternatives,the regenerative medicine landscape is shifting towards genome engineering technologies,particularly gene editing.Clustered regularly interspaced short palindromic repeats(CRISPR)-based gene editing systems enable precise knock-ins,knockouts,transcriptional activation and repression,as well as specific base conversions.This advancement has allowed researchers to treat genetic and degenerative diseases,control cell fate for highly regulated tissue repair,and enhance tissue functions.In this review,we explore the progress and future prospects of CRISPR technologies in regenerative medicine,focusing on how gene editing has led to advanced therapeutic applications and served as a versatile research tool for understanding tissue development and disease progression.展开更多
Tomato,a vegetable of considerable global significance,has been the subject of extensive breeding efforts primarily aimed at achieving high yields and resistance to multiple stressors.However,despite these endeavors,t...Tomato,a vegetable of considerable global significance,has been the subject of extensive breeding efforts primarily aimed at achieving high yields and resistance to multiple stressors.However,despite these endeavors,the quality of fruits still cannot fully satisfy the diverse preferences of the majority of consumers.The elucidation of genetic determinants underlying fruit quality traits,coupled with the advancement of gene editing techniques,has significantly contributed to the enhancement of tomato quality.Combining with gene editing technology to improve tomato fruit quality traits represents a viable approach for maximizing the utilization of essential genes in breeding programs.This review provides a comprehensive summary of the significant genes associated with tomato fruit quality traits,as well as an overview of the current advancements and potential avenues for enhancing tomato quality through gene editing technology.Four important aspects of fruit qualitydappearance,flavor,nutritional profiles and postharvest properties form the basis of the review,providing a thorough update on the state of research in tomato fruit quality improvement via new gene editing techniques.展开更多
CRISPR/Cas9 technology, a revolutionary gene-editing tool, has rapidly garnered attention in plant science owing to its simplicity, high editing efficiency, and cost-effectiveness. Besides, it offers unprecedented pre...CRISPR/Cas9 technology, a revolutionary gene-editing tool, has rapidly garnered attention in plant science owing to its simplicity, high editing efficiency, and cost-effectiveness. Besides, it offers unprecedented precision and efficiency in the genetic improvement of fruit trees. To date, this technology has been widely utilized to enhance fruit quality, improve stress resistance, and mediate growth and development. These applications demonstrate its immense potential in fruit tree breeding. Looking ahead, advancements in editing efficiency, expanded application scopes, comprehensive safety assessments, and improved regulatory frameworks are expected to further broaden the role of CRISPR/Cas9 in fruit tree breeding, thereby driving the fruit tree industry toward higher yield, superior quality, enhanced stress resilience, higher efficiency, and contributing to global food security and sustainable agricultural development. This article outlines the fundamental principles of CRISPR/Cas9 gene editing technology, its applications in plants (including fruit trees), and its pivotal role in genetic improvement and germplasm innovation.展开更多
Nonobstructive azoospermia(NOA)affects about 60%of men with azoospermia,representing a severe form of male infertility.The current approach to manage NOA primarily involves testicular sperm retrieval methods such as c...Nonobstructive azoospermia(NOA)affects about 60%of men with azoospermia,representing a severe form of male infertility.The current approach to manage NOA primarily involves testicular sperm retrieval methods such as conventional testicular sperm extraction(c-TESE)and microdissection testicular sperm extraction(micro-TESE).While combining testicular sperm retrieval with intracytoplasmic sperm injection(ICSI)offers hope for patients,the overall sperm retrieval rate(SRR)stands at around 50%.In cases where micro-TESE fails to retrieve sperm,limited options,like donor sperm or adoption,can be problematic in certain cultural contexts.This paper delves into prospective treatments for NOA management.Gene editing technologies,particularly clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated(Cas)protein 9(CRISPR/Cas9),hold potential for correcting genetic mutations underlying testicular dysfunction.However,these technologies face challenges due to their complexity,potential off-target effects,ethical concerns,and affordability.This calls for research to address key challenges associated with NOA management within the clinical settings.This also necessitate ongoing research essential for developing more sensitive diagnostic tests,validating novel treatments,and customizing current treatment strategies for individual patients.This review concluded that the future of NOA management may entail a combination of these treatment options,tailored to each patient’s unique circumstances,providing a comprehensive approach to address NOA challenges.展开更多
Ectothermic organisms may expand their thermal tolerance by producing multiple protein isoforms with differing thermal sensitivities.While such isoforms commonly originate from allelic variation at a single locus(allo...Ectothermic organisms may expand their thermal tolerance by producing multiple protein isoforms with differing thermal sensitivities.While such isoforms commonly originate from allelic variation at a single locus(allozymes)or from gene duplication that gives rise to paralogs with distinct thermal responses,this study investigated mRNA editing as an alternative,post-transcriptional mechanism for generating mRNA variants.Cytosolic malate dehydrogenase(cMDH)was examined in foot tissue of two congeners of the marine mussel genus Mytilus,which occupy different thermal environments.Multiple editing events were detected within the mRNA coding region in both species.Editing sites were species-specific,with no shared positions identified.In M.coruscus,editing occurred at 117,123,135,190,195,204,279,and 444,while in M.galloprovincialis,editing was detected at 216 and 597.Each species exhibited multiple edited mRNA variants,and these isoforms were associated with differential protein expression.These findings suggest that mRNA editing may contribute an additional layer of molecular variation.The generation of diverse mRNA isoforms from a single DNA coding sequence may enhance enzymatic flexibility across temperature ranges,supporting eurythermal physiological performance and mitigating thermal stress.Moreover,the presence of multiple edited transcripts within individual organisms raises important caveats about the limitations of approaches that deduce amino acid sequences or estimate adaptive variation solely from genomic data.展开更多
The pervasive use of photo editing applications such as Photoshop and FaceTune has significantly altered societal beauty standards, particularly for individuals with skin of color, often leading to unrealistic expecta...The pervasive use of photo editing applications such as Photoshop and FaceTune has significantly altered societal beauty standards, particularly for individuals with skin of color, often leading to unrealistic expectations regarding skin appearance and health. These tools allow users to smooth skin textures, lighten skin tones, and erase imperfections, perpetuating Eurocentric beauty ideals that frequently marginalize the natural diversity of skin tones and textures. Consequently, individuals with skin of color may seek dermatological interventions—such as skin lightening treatments, aggressive acne scar revisions, and other cosmetic procedures—aimed at achieving appearances that align more closely with digitally manipulated images. This pursuit of an unattainable aesthetic can result in increased dissatisfaction with common skin conditions like hyperpigmentation and keloids, which are often misrepresented in edited photos. Additionally, the psychological impact of these alterations can exacerbate feelings of inadequacy, contributing to conditions such as anxiety and body dysmorphic disorder. Dermatologists face the dual challenge of addressing patients’ clinical needs while also managing their expectations shaped by digital enhancements. To combat this, it is essential for dermatologists to integrate patient education that emphasizes the beauty of diverse skin tones and the discrepancies between digital images and authentic skin health. By fostering an understanding of realistic outcomes and promoting the acceptance of natural skin characteristics, dermatologists can empower individuals with skin of color to prioritize authentic skin health over digitally influenced ideals, ultimately leading to more satisfying dermatological care and improved self-image.展开更多
Brassica napus,one of the most important oil crops cultivated globally,is severely impacted by prolonged soil contamination with cadmium(Cd),resulting in decreased yields and poor seed quality.This crop exhibits a hig...Brassica napus,one of the most important oil crops cultivated globally,is severely impacted by prolonged soil contamination with cadmium(Cd),resulting in decreased yields and poor seed quality.This crop exhibits a high adsorption capacity for Cd,making creating seed resources with low Cd accumulation an essential strategy to alleviate this challenge.To address this issue,we genetically edited BnaNRAMP1 in B.napus by targeting three different exon regions,resulting in new germplasm resources with significant differences in Cd accumulation capacity and unaffected yield.Among these,the mutant K140-22,specifically targeting the 7th exon,is distinguished by its substantially reduced Cd accumulation.Further,enzyme assays of the antioxidant defense system in both roots and shoots of K140-22 revealed its enhanced antioxidant activity,which contributes to elucidating the molecular mechanisms of plant tolerance to heavy metal stress.Remarkably,this mutant also maintained equivalent agronomic traits and seed quality,which highlights its potential as a germplasm resource for rapeseed breeding for low Cd accumulation and elevating rapeseed economic value in Cd-contaminated soil.展开更多
In the process of machine translation,pre-editing is a crucial step,which can help reduce the cost of post-translation editing and improve the quality of machine translation.By sorting out and reviewing the relevant l...In the process of machine translation,pre-editing is a crucial step,which can help reduce the cost of post-translation editing and improve the quality of machine translation.By sorting out and reviewing the relevant literature about pre-editing of machine translation,this paper summarizes the previous researches on pre-editing of machine translation from three aspects:the theoretical framework,automated and semi-automated pre-translation editing and evaluation of pre-translation editing effect.The possible development direction of pre-translation edting is also put forward.展开更多
Gastric cancer(GC)remains one of the leading causes of cancer-related mortality worldwide,necessitating innovative approaches for its diagnosis and treatment.Clustered regularly interspaced short palindromic repeats(C...Gastric cancer(GC)remains one of the leading causes of cancer-related mortality worldwide,necessitating innovative approaches for its diagnosis and treatment.Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPRassociated protein 9(Cas9),a revolutionary gene-editing technology,has emerged as a powerful tool for unraveling the molecular mechanisms underlying GC and for advancing precision medicine strategies.This review explores the current applications of CRISPR/Cas9 in GC research,including the identification of oncogenes and tumor suppressors,modeling tumor microenvironment interactions,and developing gene-based therapies.We highlight recent breakthroughs in genome editing that have enhanced our understanding of GC pathogenesis and resistance mechanisms to conventional therapies.Additionally,we discuss the potential of CRISPR/Cas9 for therapeutic gene editing in GC,addressing challenges such as off-target effects,delivery methods,and ethical considerations.By summarizing the progress and limitations of CRISPR/Cas9 in GC,this review aims to provide a comprehensive perspective on how this transformative technology could shape future strategies for the prevention,diagnosis,and treatment of GC.展开更多
基金supported by a sub-award to the University of Missouri from the Heinrich Heine University of Dusseldorf funded by the Bill&Melinda Gates Foundation(OPP1155704)(Bing Yang)and the China Scholar Council(Chenhao Li,as a joint Ph.D.student).
文摘Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.
基金supported by the National Natural Science Foundation of China(82404798)the Natural Science Foundation of Sichuan Province(2024NSFSC1831)+1 种基金the National Key Laboratory for Tropical Crop Breeding(NKLTCB-RC202403,NKLTCBZRJJ4)the Hainan Seed Industrial Laboratory(B22C1000P).
文摘Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present the development and evaluation of a novel glycosylase-based cytosine base editor(gCBE)for efficient C-to-G editing in rice.Unlike traditional cytosine base editors,which rely on cytosine deamination,gCBE directly excises cytosine to generate an apurinic/apyrimidinic(AP)site,thus circumventing the deamination step and reducing the production of C-to-T byproducts.We constructed several gCBE variants,including N-gCBE,M-gCBE,and C-gCBE,by fusing engineered human UDG2(UNG*)to SpCas9 nickase(nSpCas9,D10A)and tested their editing efficiency and specificity in rice.Our results demonstrate that M-gCBE achieved efficient C-to-G editing(6.3%to 37.5%)similar to OsCGBE(9.4%to 28.1%)at most targets,though with site-dependent variations.Notably,gCBE tools showed a marked reduction in C-to-T byproducts,with average C-to-T mutation rates of 12.5%for N-gCBE and 16.7%for M-gCBE,compared to 53.1%for OsCGBE.Notably,both N-gCBE and M-gCBE were capable of generating homozygous C-to-G mutations in the T_(0)generation,a key advantage over OsCGBE,which predominantly generated C-to-T mutations.Off-target analysis revealed minimal off-target effects with M-gCBE,highlighting its potential for high-precision genome editing.These findings suggest that gCBE tools,particularly M-gCBE,are highly efficient and precise,providing an advanced solution for C-to-G editing in plants and offering promising applications for crop improvement.
基金funded by the National Natural Science Foundation of China(32200208 to J-PG,and 32170250 to JDM)J-PG is supported by a grant to the University of Cambridge by the Bill&Melinda Gates Foundation and the UK Foreign,Commonwealth and Development Office(OPP1028264)known as the Enabling Nutrient Symbioses in Agriculture(ENSA)projectYS is supported by the China Scholarship Council(202208310095).
文摘The advent of genome editing technologies,particularly CRISPR/Cas9,has significantly advanced the generation of legume mutants for reverse genetic studies and understanding the mechanics of the rhizobial symbiosis.The legume–rhizobia symbiosis is crucial for sustainable agriculture,enhancing nitrogen fixation and improving soil fertility.Numerous genes with a symbiosis-specific expression have been identified,sometimes exclusively expressed in cells forming infection threads or in nitrogen-fixing nodule cells.Typically,mutations in these genes do not affect plant growth.However,in some instances,germline homozygous mutations can be lethal or result in complex pleiotropic phenotypes that are challenging to interpret.To address this issue,a rhizobia-inducible and cell-type-specific CRISPR/Cas9 strategy was developed to knock-out genes in specific legume transgenic root tissues.In this review,we discuss recent advancements in legume genome editing,highlighting the cell-type-specific CRISPR system and its crucial applications in symbiotic nitrogen fixation and beyond.
基金financially supported by the National Natural Science Foundation of China(No.52473097)the Fundamental Research Funds for the Central Universities(No.24X010301678)Shanghai Jiao Tong University 2030 Initiative(No.WH510363002/002)。
文摘Incorporating a low density of ester units into the backbone of polyethylene materials enhances their sustainability and recyclability while maintaining the main material properties of polyethylenes.Here we report a new way to access degradable polyethylene materials with a low content of in-chain ester units via mechanochemical backbone editing.Initially,ester groups are incorporated as side groups through catalytic copolymerization of ethylene with a cyclobutene-fused lactone monomer(CBL),yielding polyethylene materials with high molecular weights and adjustable thermomechanical properties.Subsequent solid-state ball-milling treatment selectively introduces side-chain ester groups into the main chain of the polyethylene materials via force-induced cycloreversion of the cyclobutane units.Under acidic conditions,hydrolysis of the resultant polyethylene materials with in-chain ester units facilitates further degradation into oligomers.
文摘The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical limitations persist in current computational tools for quantifying editing efficiency-particularly concerning data processing capabilities,analytical throughput,and operational flexibility.This research presents SuperDecode,a novel computational framework designed to address these methodological constraints.The SuperDecode offers key advantages,including local processing capabilities,large-size sequencing files,batch-processing,and diversified operational functions.
文摘Precise chromosome engineering has traditionally relied on the Cre-Lox recombination system-an approach in which the enzyme Cre functions like molecular scissors,cutting and rejoining DNA at specific“Lox”sites to add,remove,or flip genomic DNA segments inside living cells.
基金supported by the Agricultural Gongguan Project of Xinjiang Production and Construction Corps,China(NYHXGG,2023AA102)the Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-CSIAF-202402)+1 种基金the Outstanding Youth Foundation of Henan Scientific Committee,China(222300420097)the China Agriculture Research System of MOF and MARA(CARS-15-02).
文摘Genome editing in plants is a powerful strategy that can substantially advance functional genomics research,facilitating the discovery,enhancement,and development of novel traits with significant agricultural implications.Various methodologies,such as zinc finger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),and CRISPR/Cas systems,have been developed for this purpose.
基金funded by the National Key Research and Development Program of China(2023YFC2506100)the National Natural Science Foundation of China(31971365,32371509,32001063,and 82271688)+3 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2019BT02Y276)the Guangdong Basic and Applied Basic Research Foundation(2023A1515010176)the grant from MOE Key Laboratory of Gene Function and Regulation,the Guangzhou Science and Technology Planning Project(2023A04J1952)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(23ptpy59).
文摘Mutations in the Rhodopsin(RHO)gene are the main cause of autosomal dominant retinitis pigmentosa(adRP),84%of which are pathogenic gain-of-function point mutations.Treatment strategies for adRP typically involve silencing or ablating the pathogenic allele,while normal RHO protein replacement has no meaningful therapeutic benefit.Here,we present an adenine base editor(ABE)-mediated therapeutic approach for adRP caused by RHO point mutations in vivo.The correctable pathogenic mutations are screened and verified,including T17M,Q344ter,and P347L.Two adRP animal models are created carrying the class 1(Q344ter)and class 2(T17M)mutations,and dual AAV-delivered ABE can effectively repair both mutations in vivo.The early intervention of ABE8e efficiently corrects the Q344ter mutation that causes a severe form of adRP,delays photoreceptor death,and restores retinal function and visual behavior.These results suggest that ABE is a promising alternative to treat RHO mutation-associated adRP.Our work provides an effective spacer-mediated point mutation correction therapy for dominantly inherited ocular disorders.
基金supported by Funding was provided by grants from the Changsha Chinese Medicine Foundation(Grant No.B202314)the Natural Science Foundation of Hunan Province,China(Grant No.2024JJ8224)+1 种基金Changsha Municipal Natural Science Foundation(Grant No.kq2403187)Hunan Province Children’s Safe Medication Clinical Medical Technology Demonstration Base(Grant No.2023SK4083).
文摘Pediatric congenital heart disease(CHD)pharmacotherapy faces three fundamental barriers:developmental pharmacokinetic complexity,anatomic-genetic heterogeneity,and evidence chain gaps.Traditional agents exhibit critical limitations:digoxin’s narrow therapeutic index(0.5–0.9 ng/mL)is exacerbated by ABCB1 mutations(toxicity risk increases 4.1-fold),furosemide efficacy declines by 35%in neonates due to NKCC2 immaturity,andβ-blocker responses vary by CYP2D6 polymorphisms(poor metabolizers require 50–75%dose reduction).Novel strategies demonstrate transformative potential—CRISPR editing achieves 81%reversal of BMPR2-associated pulmonary vascular remodeling,metabolically matured cardiac organoids replicate adult myocardial energy metabolism for drug screening,and SGLT2 inhibitors activate triple mechanisms(calcium overload mitigation,mitophagy,fibrosis reversal).However,clinical translation requires overcoming developmental barriers:age-dependent enzyme expression(infant CYP2D6=30–60%adult activity),post-Fontan hepatotoxicity(bosentan trough concentrations elevates 1.8-fold),and AI model limitations(32%error in complex CHD).Future integration of placental transfer models,disease-specific organoids,and multi-omics mapping of FOXO/CRIM1 pathways will shift paradigms from symptom control to curative repair.
基金supported by Jilin Provincial Department of Education(JKH20230394KJ).
文摘Clustered regularly interspaced short palindromic repeat sequences(CRISPR)and their accompanying proteins(Cas),commonly presenting in bacteria and archaea,make up the CRISPR/Cas system.As one of the funda-mental sources of nutrition for humans,edible crops play a crucial role in ensuring global food security.CRISPR/Cas9 gene editing has been applied to improve many crop traits,such as increasing nitrogen utilization efficiency,creating male sterile germplasm,and regulating tiller and spikelet formation.This paper provides a comprehensive overview of the use of CRISPR/Cas gene editing technology in crop genomes,covering the targeted genes,the types of editing that take place,the mechanism of action.Finally,we also discussed the efficiency of gene editing and pointed the future direction on how to speed up crop molecular breeding,increase breeding effectiveness,and produce more new crop varieties with high qualities.
基金supported by the National Natural Science Foundation of China(Nos.21804059 and 21701059)the Natural Science Foundation of Jiangsu Province(No.BK20180974)+1 种基金the China Postdoctoral Science Foundation(No.2020M681544)the Postdoctoral Science Foundation of Jiangsu Province(No.2020Z351)。
文摘As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.
基金supported by the National Institutes of Health(UH3NS115598).
文摘The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional regenerative medicine and tissue engineering strategies have created specialized tissues using progenitor cells and various biological stimuli.To date,there are many US Food and Drug Administration(FDA)-approved regenerative medicine therapies,such as those for wound healing and orthopedic injuries.Nonetheless,these therapies face challenges,including off-target effects,a lack of precision,and failure to target the disease or injury at its origin.In search of novel,precise,and efficient alternatives,the regenerative medicine landscape is shifting towards genome engineering technologies,particularly gene editing.Clustered regularly interspaced short palindromic repeats(CRISPR)-based gene editing systems enable precise knock-ins,knockouts,transcriptional activation and repression,as well as specific base conversions.This advancement has allowed researchers to treat genetic and degenerative diseases,control cell fate for highly regulated tissue repair,and enhance tissue functions.In this review,we explore the progress and future prospects of CRISPR technologies in regenerative medicine,focusing on how gene editing has led to advanced therapeutic applications and served as a versatile research tool for understanding tissue development and disease progression.
基金supported by grants from the National Key Research&Development Plan(Grant Nos.2022YFD1200502,2021YFD1200201)National Natural Science Foundation of China(Grant Nos.32372696,31991182)+6 种基金Wuhan Biological Breeding Major Project(Grant No.2022021302024852)HZAU-AGIS Cooperation Fund(Grant No.SZYJY2023022)Funds for High Quality Development of Hubei Seed Industry(Grant No.HBZY2023B004)Hubei Agriculture Research System(Grant No.2023HBSTX4-06)Hubei Key Research&Development Plan(Grant Nos.2022BBA0066,2022BBA0062)Funds of National Key Laboratory for Germplasm Innovation&Utilization of Horticultural Crops(Grant No.Horti-3Y-2024-008)Key Project of Hubei Hongshan Laboratory(Grant No.2021hszd007).
文摘Tomato,a vegetable of considerable global significance,has been the subject of extensive breeding efforts primarily aimed at achieving high yields and resistance to multiple stressors.However,despite these endeavors,the quality of fruits still cannot fully satisfy the diverse preferences of the majority of consumers.The elucidation of genetic determinants underlying fruit quality traits,coupled with the advancement of gene editing techniques,has significantly contributed to the enhancement of tomato quality.Combining with gene editing technology to improve tomato fruit quality traits represents a viable approach for maximizing the utilization of essential genes in breeding programs.This review provides a comprehensive summary of the significant genes associated with tomato fruit quality traits,as well as an overview of the current advancements and potential avenues for enhancing tomato quality through gene editing technology.Four important aspects of fruit qualitydappearance,flavor,nutritional profiles and postharvest properties form the basis of the review,providing a thorough update on the state of research in tomato fruit quality improvement via new gene editing techniques.
基金Supported by Scientific Research Start-up Fund for PhD.of Zhaoqing University(210046)the Zhaoqing Science and Technology Innovation Guidance Project(231017174162871,241226220091239).
文摘CRISPR/Cas9 technology, a revolutionary gene-editing tool, has rapidly garnered attention in plant science owing to its simplicity, high editing efficiency, and cost-effectiveness. Besides, it offers unprecedented precision and efficiency in the genetic improvement of fruit trees. To date, this technology has been widely utilized to enhance fruit quality, improve stress resistance, and mediate growth and development. These applications demonstrate its immense potential in fruit tree breeding. Looking ahead, advancements in editing efficiency, expanded application scopes, comprehensive safety assessments, and improved regulatory frameworks are expected to further broaden the role of CRISPR/Cas9 in fruit tree breeding, thereby driving the fruit tree industry toward higher yield, superior quality, enhanced stress resilience, higher efficiency, and contributing to global food security and sustainable agricultural development. This article outlines the fundamental principles of CRISPR/Cas9 gene editing technology, its applications in plants (including fruit trees), and its pivotal role in genetic improvement and germplasm innovation.
文摘Nonobstructive azoospermia(NOA)affects about 60%of men with azoospermia,representing a severe form of male infertility.The current approach to manage NOA primarily involves testicular sperm retrieval methods such as conventional testicular sperm extraction(c-TESE)and microdissection testicular sperm extraction(micro-TESE).While combining testicular sperm retrieval with intracytoplasmic sperm injection(ICSI)offers hope for patients,the overall sperm retrieval rate(SRR)stands at around 50%.In cases where micro-TESE fails to retrieve sperm,limited options,like donor sperm or adoption,can be problematic in certain cultural contexts.This paper delves into prospective treatments for NOA management.Gene editing technologies,particularly clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated(Cas)protein 9(CRISPR/Cas9),hold potential for correcting genetic mutations underlying testicular dysfunction.However,these technologies face challenges due to their complexity,potential off-target effects,ethical concerns,and affordability.This calls for research to address key challenges associated with NOA management within the clinical settings.This also necessitate ongoing research essential for developing more sensitive diagnostic tests,validating novel treatments,and customizing current treatment strategies for individual patients.This review concluded that the future of NOA management may entail a combination of these treatment options,tailored to each patient’s unique circumstances,providing a comprehensive approach to address NOA challenges.
基金supported by the National Key Research and Development Program of China(2022-24)National Natural Science Foundation of China(42025604,42376102)Fundamental Research Funds for the Central Universities。
文摘Ectothermic organisms may expand their thermal tolerance by producing multiple protein isoforms with differing thermal sensitivities.While such isoforms commonly originate from allelic variation at a single locus(allozymes)or from gene duplication that gives rise to paralogs with distinct thermal responses,this study investigated mRNA editing as an alternative,post-transcriptional mechanism for generating mRNA variants.Cytosolic malate dehydrogenase(cMDH)was examined in foot tissue of two congeners of the marine mussel genus Mytilus,which occupy different thermal environments.Multiple editing events were detected within the mRNA coding region in both species.Editing sites were species-specific,with no shared positions identified.In M.coruscus,editing occurred at 117,123,135,190,195,204,279,and 444,while in M.galloprovincialis,editing was detected at 216 and 597.Each species exhibited multiple edited mRNA variants,and these isoforms were associated with differential protein expression.These findings suggest that mRNA editing may contribute an additional layer of molecular variation.The generation of diverse mRNA isoforms from a single DNA coding sequence may enhance enzymatic flexibility across temperature ranges,supporting eurythermal physiological performance and mitigating thermal stress.Moreover,the presence of multiple edited transcripts within individual organisms raises important caveats about the limitations of approaches that deduce amino acid sequences or estimate adaptive variation solely from genomic data.
文摘The pervasive use of photo editing applications such as Photoshop and FaceTune has significantly altered societal beauty standards, particularly for individuals with skin of color, often leading to unrealistic expectations regarding skin appearance and health. These tools allow users to smooth skin textures, lighten skin tones, and erase imperfections, perpetuating Eurocentric beauty ideals that frequently marginalize the natural diversity of skin tones and textures. Consequently, individuals with skin of color may seek dermatological interventions—such as skin lightening treatments, aggressive acne scar revisions, and other cosmetic procedures—aimed at achieving appearances that align more closely with digitally manipulated images. This pursuit of an unattainable aesthetic can result in increased dissatisfaction with common skin conditions like hyperpigmentation and keloids, which are often misrepresented in edited photos. Additionally, the psychological impact of these alterations can exacerbate feelings of inadequacy, contributing to conditions such as anxiety and body dysmorphic disorder. Dermatologists face the dual challenge of addressing patients’ clinical needs while also managing their expectations shaped by digital enhancements. To combat this, it is essential for dermatologists to integrate patient education that emphasizes the beauty of diverse skin tones and the discrepancies between digital images and authentic skin health. By fostering an understanding of realistic outcomes and promoting the acceptance of natural skin characteristics, dermatologists can empower individuals with skin of color to prioritize authentic skin health over digitally influenced ideals, ultimately leading to more satisfying dermatological care and improved self-image.
基金supported by the National Key Research and Development Program of China(2022YFD1601502 and 2023YFD1200202)the National Natural Science Foundation of China(32272167 and 32341028)+1 种基金the Sichuan Science and Technology Program,China(2022ZDZX0015)the Fundamental Research Funds for the Central Universities,China(SCU2019D013)。
文摘Brassica napus,one of the most important oil crops cultivated globally,is severely impacted by prolonged soil contamination with cadmium(Cd),resulting in decreased yields and poor seed quality.This crop exhibits a high adsorption capacity for Cd,making creating seed resources with low Cd accumulation an essential strategy to alleviate this challenge.To address this issue,we genetically edited BnaNRAMP1 in B.napus by targeting three different exon regions,resulting in new germplasm resources with significant differences in Cd accumulation capacity and unaffected yield.Among these,the mutant K140-22,specifically targeting the 7th exon,is distinguished by its substantially reduced Cd accumulation.Further,enzyme assays of the antioxidant defense system in both roots and shoots of K140-22 revealed its enhanced antioxidant activity,which contributes to elucidating the molecular mechanisms of plant tolerance to heavy metal stress.Remarkably,this mutant also maintained equivalent agronomic traits and seed quality,which highlights its potential as a germplasm resource for rapeseed breeding for low Cd accumulation and elevating rapeseed economic value in Cd-contaminated soil.
文摘In the process of machine translation,pre-editing is a crucial step,which can help reduce the cost of post-translation editing and improve the quality of machine translation.By sorting out and reviewing the relevant literature about pre-editing of machine translation,this paper summarizes the previous researches on pre-editing of machine translation from three aspects:the theoretical framework,automated and semi-automated pre-translation editing and evaluation of pre-translation editing effect.The possible development direction of pre-translation edting is also put forward.
文摘Gastric cancer(GC)remains one of the leading causes of cancer-related mortality worldwide,necessitating innovative approaches for its diagnosis and treatment.Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPRassociated protein 9(Cas9),a revolutionary gene-editing technology,has emerged as a powerful tool for unraveling the molecular mechanisms underlying GC and for advancing precision medicine strategies.This review explores the current applications of CRISPR/Cas9 in GC research,including the identification of oncogenes and tumor suppressors,modeling tumor microenvironment interactions,and developing gene-based therapies.We highlight recent breakthroughs in genome editing that have enhanced our understanding of GC pathogenesis and resistance mechanisms to conventional therapies.Additionally,we discuss the potential of CRISPR/Cas9 for therapeutic gene editing in GC,addressing challenges such as off-target effects,delivery methods,and ethical considerations.By summarizing the progress and limitations of CRISPR/Cas9 in GC,this review aims to provide a comprehensive perspective on how this transformative technology could shape future strategies for the prevention,diagnosis,and treatment of GC.
