Extensive humoral immune response to AAVs and Cas proteins in nonhuman primates

• 作 者: Puhao Xiao Raoxian Bai Ting Zhang Ruo Wu Lijiao Chen Yu Hou Bin Shen Yuyu Niu Shangang Li Weizhi Ji Yongchang Chen
• 机 构: State Key Laboratory of Primate Biomedical Research;Institute of Primate Translational Medicine,Kunm
• 出 处: 科学通报（英文版）
• 发表日期: 2021年20期

Gene therapy is expected to fundamentally correct mutant genes to cure genetic diseases in vivo.As a delivery system for gene therapy,adenovirus-associated virus (AAV) vectors have achieved positive results in clinical and preclinical research,including the treatment of genetic diseases,such as those affecting the blood and eyes [1].The clustered regularly interspaced short palindromic repeats (CRISPR) system has ignited high hopes for gene therapy since its emergence,especially Cas9 and Casl2a (Cpf1),which exhibit both the right size and efficient editing capacity [2-4].Recently,the CRISPR system has been successfully applied to mam-malian gene therapy and has gradually become the most promising strategy for gene repair [5-7].In general,immune problems have rarely been considered in experiments including primates.In pri-mates,the natural host of AAV,the presence of pre-existing anti-bodies greatly weakens the delivery process of AAV and can even cause the complete failure of gene therapy [8,9].In addition,sev-eral research teams have reported that adaptive immunity against the CRISPR effector Cas9 nuclease is ubiquitous in humans,and the immunogenicity of Cas9 also poses a challenge to gene therapy based on the CRISPR system [10,11].However,there has been no comprehensive evaluation of the immune response of AAV and Cas9 for in vivo experiments in primates.