The clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a...The clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs(sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies.Moreover, CRISPR-Cas9 systems have been used to partially or completely alleviate disease symptoms by mutating or correcting related genes. However, the efficient transfer of CRISPR-Cas9 system into cells and target organs remains a challenge that affects the robust and precise genome editing activity. The current review focuses on delivery systems for Cas9 mRNA, Cas9 protein, or vectors encoding the Cas9 gene and corresponding sgRNA. Non-viral delivery of Cas9 appears to help Cas9 maintain its on-target effect and reduce off-target effects, and viral vectors for sgRNA and donor template can improve the efficacy of genome editing and homology-directed repair. Safe, efficient, and producible delivery systems will promote the application of CRISPR-Cas9 technology in human gene therapy.展开更多
It is surprising that,while arsenic trioxide(ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia(APL)",the most important discoverer remains obscure and his ...It is surprising that,while arsenic trioxide(ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia(APL)",the most important discoverer remains obscure and his original papers have not been cited by a single English paper.The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive.Beginning with recipes from a countryside practitioner that were vague in applicable diseases,Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL.More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively.Other researchers,first in China and then in the West,followed his lead.Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target.Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required.Publication of Western replication in 1998 made the therapy widely accepted,though neither Western,nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s.This article focuses on the early papers of Zhang,but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers,and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients.展开更多
基金supported by the National Natural and Scientific Foundation of China (81602699 to Zhi-Yao He, 81502677 to Ke Men, 81402302 to Yang Yang)the National High Technology Research and Development Program of China (2015AA020309 to Zhi-Yao He)the China Postdoctoral Science Foundation Funded Project (2015M570791 to Zhi-Yao He)
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs(sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies.Moreover, CRISPR-Cas9 systems have been used to partially or completely alleviate disease symptoms by mutating or correcting related genes. However, the efficient transfer of CRISPR-Cas9 system into cells and target organs remains a challenge that affects the robust and precise genome editing activity. The current review focuses on delivery systems for Cas9 mRNA, Cas9 protein, or vectors encoding the Cas9 gene and corresponding sgRNA. Non-viral delivery of Cas9 appears to help Cas9 maintain its on-target effect and reduce off-target effects, and viral vectors for sgRNA and donor template can improve the efficacy of genome editing and homology-directed repair. Safe, efficient, and producible delivery systems will promote the application of CRISPR-Cas9 technology in human gene therapy.
文摘It is surprising that,while arsenic trioxide(ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia(APL)",the most important discoverer remains obscure and his original papers have not been cited by a single English paper.The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive.Beginning with recipes from a countryside practitioner that were vague in applicable diseases,Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL.More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively.Other researchers,first in China and then in the West,followed his lead.Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target.Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required.Publication of Western replication in 1998 made the therapy widely accepted,though neither Western,nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s.This article focuses on the early papers of Zhang,but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers,and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients.
