The size consistency of the second and third order energies of the multireference perturbation theory(Chen F,Davidson E,Iwata S.Int J Quant Chem,2002,86:256)is investigated theoretically with a su-per-molecular model ...The size consistency of the second and third order energies of the multireference perturbation theory(Chen F,Davidson E,Iwata S.Int J Quant Chem,2002,86:256)is investigated theoretically with a su-per-molecular model composed of N-hydrogen molecules separated by a large distance.It is found that the two perturbation series corresponding to two Hamiltonian partitions are not size consistent at the second and third order.However,two size consistent forms are suggested for two Hamiltonian parti-tions at the second order,if some approximations to the denominators of the original second order energies are assumed.展开更多
Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable s...Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable synthesis techniques that can consistently produce formulations from early development to clinical application.In this work,we proposed a method to achieve scalable synthesis of LNPs by scaling inertial microfluidic mixers isometrically in three dimensions.Moreover,a theoretical predictive method,which controls the mixing time to be equal across different chips,is developed to ensure consistent particle size and size distribution of the synthesized LNPs.LNPs loaded with small interfering RNA(siRNA)were synthesized at different flow rates,exhibiting consistent physical properties,including particle size,size distribution and encapsulation efficiency.This work provides a practical approach for scalable synthesis of LNPs consistently,offering the potential to accelerate the transition of nucleic acid drug development into clinical application.展开更多
基金Supported by the National Natural Science Foundation of China(Grant No.20473011)the University of Science and Technology Beijing(Grant No.00007414)the Ministry of Education of China(Grant No.11140036)
文摘The size consistency of the second and third order energies of the multireference perturbation theory(Chen F,Davidson E,Iwata S.Int J Quant Chem,2002,86:256)is investigated theoretically with a su-per-molecular model composed of N-hydrogen molecules separated by a large distance.It is found that the two perturbation series corresponding to two Hamiltonian partitions are not size consistent at the second and third order.However,two size consistent forms are suggested for two Hamiltonian parti-tions at the second order,if some approximations to the denominators of the original second order energies are assumed.
基金supported in part by Collaborative Innovation Program of Hefei Science Center,CAS(No.2022HSCCIP001)Anhui Province Key Laboratory of High Field Magnetic Resonance Imaging(No.KFKT-2022-0003)+1 种基金Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scholars(No.51929501)National Key R&D Program of China(No.2022YFF0705002).
文摘Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable synthesis techniques that can consistently produce formulations from early development to clinical application.In this work,we proposed a method to achieve scalable synthesis of LNPs by scaling inertial microfluidic mixers isometrically in three dimensions.Moreover,a theoretical predictive method,which controls the mixing time to be equal across different chips,is developed to ensure consistent particle size and size distribution of the synthesized LNPs.LNPs loaded with small interfering RNA(siRNA)were synthesized at different flow rates,exhibiting consistent physical properties,including particle size,size distribution and encapsulation efficiency.This work provides a practical approach for scalable synthesis of LNPs consistently,offering the potential to accelerate the transition of nucleic acid drug development into clinical application.
