Antivector and antitransgene host responses in gene therapy

Area of Science:

• * Molecular Biology
• * Immunology
• * Biotechnology

Background:

• * Viral gene therapy vectors are crucial for in vivo gene transfer but often induce host immune responses against the vector or transgene.
• * These immune reactions, including cellular and humoral responses, depend on vector type, administration route, and host factors.
• * Adenoviral vectors typically cause strong, transient immune responses, while adeno-associated virus (AAV) and retrovirus vectors elicit weaker responses, enabling longer expression.

Purpose of the Study:

• * To review the impact of host immune responses on viral gene therapy efficacy.
• * To discuss strategies for mitigating immune reactions to enhance gene transfer.
• * To compare the immunogenicity of different viral vector types.

Main Methods:

• * Literature review of current viral gene therapy vectors and associated host responses.
• * Analysis of factors influencing immune reactions (vector type, administration, host genotype).
• * Evaluation of methods to overcome immune barriers in gene therapy.

Main Results:

• * Viral vectors and transgene expression invariably provoke innate and acquired host immunity.
• * Adenoviral vectors lead to potent but short-lived gene expression due to strong immune responses.
• * AAV and retroviral vectors demonstrate reduced immunogenicity, facilitating sustained gene transfer and expression.

Conclusions:

• * Host immune responses are a significant hurdle for effective and durable viral gene therapy.
• * Modifying viral vectors and employing host immunosuppression are key strategies to improve gene transfer longevity and efficiency.
• * Understanding and managing immunogenicity is critical for advancing clinical applications of gene therapy.