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
Chimeric antigen receptor （CAR） T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting t...Chimeric antigen receptor （CAR） T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or ＂on-target/off-tumor＂ toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strafegies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vecfor designs to increase both the safety and efficacy, further T cell modification to overcome the tumorassociated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal--curing cancer with high safety, high efficacy, and low cost.展开更多
Precise modifications of complex genomes at the single nucleotide level have been one of the big goals for scientists working in basic and applied genetics,including biotechnology,drug development,gene therapy and syn...Precise modifications of complex genomes at the single nucleotide level have been one of the big goals for scientists working in basic and applied genetics,including biotechnology,drug development,gene therapy and synthetic biology.However,the relevant techniques for making these manipulations in model organisms and human cells have been lagging behind the rapid high throughput studies in the post-genomic era with a bottleneck of low efficiency,time consuming and laborious manipulation,and off-targeting problems.Recent discoveries of TALEs（transcription activator-like effectors） coding system and CRISPR（clusters of regularly interspaced short palindromic repeats） immune system in bacteria have enabled the development of customized TALENs（transcription activator-like effector nucleases） and CRISPR/Cas9 to rapidly edit genomic DNA in a variety of cell types,including human cells,and different model organisms at a very high efficiency and specificity.In this review,we first briefly summarize the development and applications of TALENs and CRISPR/Cas9-mediated genome editing technologies;compare the advantages and constraints of each method;particularly,discuss the expected applications of both techniques in the field of site-specific genome modification and stem cell based gene therapy;finally, propose the future directions and perspectives for readers to make the choices.展开更多
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).
文摘Chimeric antigen receptor （CAR） T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or ＂on-target/off-tumor＂ toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strafegies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vecfor designs to increase both the safety and efficacy, further T cell modification to overcome the tumorassociated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal--curing cancer with high safety, high efficacy, and low cost.
基金supported financially by the National Basic Research Program of China(973 Program)(Nos. 2009CB918702 and 2012CB825504)the National Natural Science Foundation of China(Nos.31201007,31271573 and 31071087)
文摘Precise modifications of complex genomes at the single nucleotide level have been one of the big goals for scientists working in basic and applied genetics,including biotechnology,drug development,gene therapy and synthetic biology.However,the relevant techniques for making these manipulations in model organisms and human cells have been lagging behind the rapid high throughput studies in the post-genomic era with a bottleneck of low efficiency,time consuming and laborious manipulation,and off-targeting problems.Recent discoveries of TALEs（transcription activator-like effectors） coding system and CRISPR（clusters of regularly interspaced short palindromic repeats） immune system in bacteria have enabled the development of customized TALENs（transcription activator-like effector nucleases） and CRISPR/Cas9 to rapidly edit genomic DNA in a variety of cell types,including human cells,and different model organisms at a very high efficiency and specificity.In this review,we first briefly summarize the development and applications of TALENs and CRISPR/Cas9-mediated genome editing technologies;compare the advantages and constraints of each method;particularly,discuss the expected applications of both techniques in the field of site-specific genome modification and stem cell based gene therapy;finally, propose the future directions and perspectives for readers to make the choices.
