Understanding AAV vector immunogenicity: from particle to patient.

Area of Science:

• Molecular Biology
• Immunology
• Gene Therapy

Background:

• Adeno-associated virus (AAV) is a promising vector for gene therapy due to its safety and efficacy.
• Recombinant AAV (rAAV) vectors are utilized in numerous gene therapies, with many approved or in late-stage development.
• Challenges like immunity, limited packaging, and transduction efficiency hinder wider rAAV application.

Purpose of the Study:

• To review the impact of immunity on rAAV vector-mediated gene therapies.
• To analyze factors influencing AAV seroprevalence and anti-AAV neutralizing antibodies (NAbs).
• To discuss clinical strategies for managing pre-existing and vector-induced anti-AAV NAbs.

Main Methods:

• Literature review focusing on AAV immunity and neutralizing antibodies.
• Analysis of factors affecting AAV seroprevalence.
• Examination of clinical approaches for managing anti-AAV NAbs.

Main Results:

• Pre-existing anti-AAV NAbs, from natural exposure or prior vector administration, can impede gene therapy efficacy.
• Understanding AAV seroprevalence is key to predicting and managing immune responses.
• Various methods exist to quantify NAbs and strategies to overcome immunity are being developed.

Conclusions:

• Immunity, particularly anti-AAV NAbs, remains a significant hurdle for widespread rAAV gene therapy adoption.
• Further research is needed to mitigate the impact of immune responses.
• Clinical strategies for managing anti-AAV NAbs are essential for advancing gene therapy.