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

Wei Miao

摘要：Viral vectors are instrumental in gene therapy and vaccination,addressing a spectrum of diseases from genetic dis-orders 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 tox-icity 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 in-nate and adaptive immunity.This understanding is crucial for devising strategies to mitigate immune responses to viral vectors,a key to advancing gene therapy.