Challenges and strategies: The immune responses in gene therapy

• Published in: Medicinal research reviews 2004-11, Vol.24 (6), p.748-761
• Main Authors: Zhou, Hai-sheng, Liu, De-pei, Liang, Chih-chuan
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; CpG motifs; gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Genetic Vectors - immunology; Humans; non-viral vectors; the immune responses; Transgenes - immunology; Viral Proteins - immunology; viral vectors
• ISSN: 0198-6325; 1098-1128
• DOI: 10.1002/med.20009

The host immune responses, including T lymphocytes mediated immune response and humoral immune responses are the important parts of the challenges in gene therapy. There are some potential immunostimulants in gene delivery systems, such as viral and non‐viral vectors. Viral gene products, transgene products, viral proteins derived from viral particles required by dead‐end infection, and CpG DNA in plasmid may play important roles in inducing the host immune responses when foreign genes are transferred into the targeted tissues. The immune responses should lead to many problems in gene therapy: transient expression of therapeutic gene, non‐efficient re‐administration of the same vectors, and severe side‐effects in clinical trials. Although RNAi may act as gene therapeutic agent for suppression of specific gene expression, little attention has been given to the potential non‐specific effects that might be induced. It was reported that small interfering RNAs (siRNAs) can induce the host interferon response following transfected to mammalian cells. Facing these challenges, a number of studies have been focused on taking measures to solve them, such as immunosuppression, selection of different administration routes and dose of the vectors, using the tissue‐specific promoters and modifying the vectors. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 6, 748–761, 2004