The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome...The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome manipulations in rabbit has been stalled for decades,severely limiting its applications in biomedical research.Novel genome editing technologies,especially CRISPR/Cas9,have remarkably enhanced precise genome manipulation in rabbits,and shown their superiority and promise for generating rabbit models of human genetic diseases.In this review,we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.展开更多
Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely relate...Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.展开更多
Gene editing nucleases(GENs),represented by CRISPR/Cas9,have become major tools in biomedical research and offer potential cures for many human diseases.Gene editing therapy(GETx)studies in animal models targeting gen...Gene editing nucleases(GENs),represented by CRISPR/Cas9,have become major tools in biomedical research and offer potential cures for many human diseases.Gene editing therapy(GETx)studies in animal models targeting genes such as proprotein convertase subtilisin/kexin type 9(PCSK9),apolipoprotein C3(APOC3),angiopoietin Like 3(ANGPTL3)and inducible degrader of the low-density lipoprotein receptor(IDOL)have demonstrated the benefits and advantages of GETx in managing atherosclerosis.Here we present our views on this brand new therapeutic option for cardiovascular diseases(CVD).展开更多
Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not t...Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.展开更多
文摘The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome manipulations in rabbit has been stalled for decades,severely limiting its applications in biomedical research.Novel genome editing technologies,especially CRISPR/Cas9,have remarkably enhanced precise genome manipulation in rabbits,and shown their superiority and promise for generating rabbit models of human genetic diseases.In this review,we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.
基金supported by a grant from the Strategic CAS Project(XDB38000000)a grant from the National Natural Science Foundation of China(81561128018).
文摘Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.
文摘Gene editing nucleases(GENs),represented by CRISPR/Cas9,have become major tools in biomedical research and offer potential cures for many human diseases.Gene editing therapy(GETx)studies in animal models targeting genes such as proprotein convertase subtilisin/kexin type 9(PCSK9),apolipoprotein C3(APOC3),angiopoietin Like 3(ANGPTL3)and inducible degrader of the low-density lipoprotein receptor(IDOL)have demonstrated the benefits and advantages of GETx in managing atherosclerosis.Here we present our views on this brand new therapeutic option for cardiovascular diseases(CVD).
基金supported by the National High Technology Research and Development Program of China(No.2015AA020104)the National Key Research and Development Program on Precision Medicine(No.2016YFC0901700)+6 种基金the National Basic Research Program of China(Nos.2011CB910204,2011CB510102,and 2010CB529200)the National Key Technology Support Program (No.2013BA1101B09)the National Key Scientific Instrument and Equipment Development Project(No.2012YQ03026108)the National Grand Program on Key Infectious Diseases(No. 2015ZX10004801)the Medical-Engineering Cross Project of Shanghai Jiao Tong University(No.YG2016MS33)the Youth Innovation Promotion Association CASthe National Institutes of Health grants(Nos.R01HL117491 and R01HL129778 to Y.E.C)
文摘Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.