Current progress of virus-mediated gene therapy-where we are and what we need  

作　　者：Wei Miao 

机构地区：[1]Beijing VJTBio Co.LTD,Beijing,China

出　　处：《感染控制(英文)》2024年第3期8-20,共13页

摘　　要：Viral vectors are instrumental in gene therapy and vaccination,addressing a spectrum of diseases from genetic disorders to cancer.Despite their promise,their clinical utility is hampered by the propensity to provoke host immune reactions,necessitating strategies to evade or suppress these responses.This review underscores the imperative for antigen-specific,sustainable solutions that enable vector re-administration,a current unmet need in medicine.We discuss the immunogenic profiles of retroviral,adenoviral,and AAV vectors,highlighting their integration risks,packaging limitations,and immunogenicity,respectively.The human Ad5 vector,while efficient in cell infection,faces significant challenges due to innate immune activation and pre-existing immunity,which can exacerbate toxicity and diminish therapeutic outcomes.The review emphasizes the complex interplay between viral vectors and the immune system,where the host’s defense mechanisms can impede therapeutic efficacy.We detail the initiation of innate responses via type I IFNs,triggered by pDCs and TLRs,and the pivotal role of NKT cells in linking innate and adaptive immunity.This understanding is crucial for devising strategies to mitigate immune responses to viral vectors,a key to advancing gene therapy.

关 键 词：viral vectors IMMUNOGENICITY gene therapy innate and adaptive immune systems immune evasion strategies 

分 类 号：R73[医药卫生—肿瘤]