In a new study published in Nature Materials,Liu et al.1 report a novel design of lipid nanoparticles(LNPs)in which multi-tailed ionizable phospholipids(iPhos)constitute the active component,and which facilitates endo...In a new study published in Nature Materials,Liu et al.1 report a novel design of lipid nanoparticles(LNPs)in which multi-tailed ionizable phospholipids(iPhos)constitute the active component,and which facilitates endosomal escape and thus improves delivery of mRNA and/or single-guide(sg)RNA for in vivo gene editing.LNPs composed of the best-performing iPhos and different helper lipids_zwitterionic lipids,ionizable cationic lipids and permanently cationic lipids-achieved selective organ targeting(SORT)and organ-specific CRISPR-Cas9 gene editing in spleen,liver,and lungs of mice,respectively.展开更多
In this report we investigated two-dimensionally triptycene end-capped QPPs in terms of their solution and solid-state behavior.For this purpose,a triphenylene based ortho-diamine decorated with two triptycenyl units ...In this report we investigated two-dimensionally triptycene end-capped QPPs in terms of their solution and solid-state behavior.For this purpose,a triphenylene based ortho-diamine decorated with two triptycenyl units as well as a phenylene diamine with two non-annulated triptycene units have been synthesized.Sequences of condensation reactions with a pyrene-based tetraketone and ortho-diamines yielded a series of QPPs and UV/Vis investigations of the corresponding compounds led to the conclusion,that the QPPs form dimers in solution,which was further supported by MALDI-TIMS-TOF-MS.Single-crystal X-ray analysis of the triply and quadruply triptycene end-capped QPPs furthermore showed shortπ-π-distances of 3.3-3.4?and a perfect shape match during the dimerization of the triply triptycenyl end-capped QPP making it possible synthon for crystal engineering.展开更多
In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They...In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They functionally characterize a number of these interactions,leveraging the information to identify promising candidate molecules for drug-repurposing.展开更多
In a recent study published in Science,1 Sun and colleagues showcase the power and potential of lung SORT LNPs,i.e.,lipid nanoparticles that upon systemic delivery in mice specifically and efficiently target cells in ...In a recent study published in Science,1 Sun and colleagues showcase the power and potential of lung SORT LNPs,i.e.,lipid nanoparticles that upon systemic delivery in mice specifically and efficiently target cells in the lung,most likely facilitated by their binding to plasma vitronectin and uptake via the vitronectin receptor.Most remarkably,when engineered to deliver a base editor,peripheral injection of SORT LNPs enabled highly efficient gene correction in lung stem cells,whole lung and trachea in a mouse model of cystic fibrosis,illustrating the enormous promise of this novel technology for human patients suffering from this devastating disease(Fig.1).展开更多
Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled rec...Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled receptors(GPCRs),each of which has a unique preference for the Gs,Gi,Gq,and G12 subfamilies.While the function of Gs-coupledβ-adrenergic receptors in beige adipocyte induction is well established,2 little is known about the function of G12-coupled GPCRs beyond its suppressive roles in white adipocyte maturation.3 In this study,we generated transgenic mice conditionally expressing a G12-coupled designer GPCR using a Cre-loxP system and investigated the potential effects of G12 signaling on adipocyte biology.展开更多
文摘In a new study published in Nature Materials,Liu et al.1 report a novel design of lipid nanoparticles(LNPs)in which multi-tailed ionizable phospholipids(iPhos)constitute the active component,and which facilitates endosomal escape and thus improves delivery of mRNA and/or single-guide(sg)RNA for in vivo gene editing.LNPs composed of the best-performing iPhos and different helper lipids_zwitterionic lipids,ionizable cationic lipids and permanently cationic lipids-achieved selective organ targeting(SORT)and organ-specific CRISPR-Cas9 gene editing in spleen,liver,and lungs of mice,respectively.
基金grateful to"Deutsche Forschungsgemeinschaft"supporting this project(SFB1249"N-heteropolycyclic compounds as functional materials"TP-A04).support by the state of Baden-Wurttemberg through bwHPC and the German Research Foundation(DFG)through grant no.INST 40/575-1 FUGG(JUSTUS 2 cluster).
文摘In this report we investigated two-dimensionally triptycene end-capped QPPs in terms of their solution and solid-state behavior.For this purpose,a triphenylene based ortho-diamine decorated with two triptycenyl units as well as a phenylene diamine with two non-annulated triptycene units have been synthesized.Sequences of condensation reactions with a pyrene-based tetraketone and ortho-diamines yielded a series of QPPs and UV/Vis investigations of the corresponding compounds led to the conclusion,that the QPPs form dimers in solution,which was further supported by MALDI-TIMS-TOF-MS.Single-crystal X-ray analysis of the triply and quadruply triptycene end-capped QPPs furthermore showed shortπ-π-distances of 3.3-3.4?and a perfect shape match during the dimerization of the triply triptycenyl end-capped QPP making it possible synthon for crystal engineering.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They functionally characterize a number of these interactions,leveraging the information to identify promising candidate molecules for drug-repurposing.
基金D.G.appreciates support by the German Research Foundation(DFG)through the DFG Collaborative Research Centers SFB1129(Projektnummer 240245660)TRR179(Projektnummer 272983813).
文摘In a recent study published in Science,1 Sun and colleagues showcase the power and potential of lung SORT LNPs,i.e.,lipid nanoparticles that upon systemic delivery in mice specifically and efficiently target cells in the lung,most likely facilitated by their binding to plasma vitronectin and uptake via the vitronectin receptor.Most remarkably,when engineered to deliver a base editor,peripheral injection of SORT LNPs enabled highly efficient gene correction in lung stem cells,whole lung and trachea in a mouse model of cystic fibrosis,illustrating the enormous promise of this novel technology for human patients suffering from this devastating disease(Fig.1).
基金This work is supported by JP20J20669(Y.O.),JP21H04791(A.I.),JP21H05113(A.I.),JPJSBP120213501(A.I.)JPJSBP120218801(A.I.),and JP21H05115(T.S.)from The Japan Society for the Promotion of Science(JSPS)JPMJPR1331(A.I.),JPMJFR215T(A.I.),JPMJMS2023(A.I.)from the Japan Science and Technology Agency(JST)+4 种基金JP19gm5910013(A.I.),JP19gm0010004(A.I.and J.A.),JP20am0101095(A.I.),JP22ama121038(A.I.)and JP22zf0127007(A.I.)from the Japan Agency for Medical Research and Development(AMED)Takeda Science Foundation(A.I.)The Uehara Memorial Foundation(A.I.)Tokyo Biochemical Research Foundation(A.I.)and Daiichi Sankyo Foundation of Life Science(A.I.).F.R.was supported by the Italian Ministry of University and Research through the Department of excellence“Faculty of Sciences”of Scuola Normale Superiore.The research leading to these results also received funding from the Italian Association for Cancer Research(AIRC)under My First AIRC Grant(MFAG)2020-ID.24317 project-P.I.Raimondi Francesco.G.S.and R.B.R.were funded by BMBF-funded de.NBI HD-HuB network,number#031A537C.
文摘Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled receptors(GPCRs),each of which has a unique preference for the Gs,Gi,Gq,and G12 subfamilies.While the function of Gs-coupledβ-adrenergic receptors in beige adipocyte induction is well established,2 little is known about the function of G12-coupled GPCRs beyond its suppressive roles in white adipocyte maturation.3 In this study,we generated transgenic mice conditionally expressing a G12-coupled designer GPCR using a Cre-loxP system and investigated the potential effects of G12 signaling on adipocyte biology.
