Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies

Area of Science:

• Biotechnology
• Gene Therapy
• Preclinical Research

Background:

• Adeno-associated virus (AAV) is a key vector for gene therapy, with numerous clinical trials and FDA approvals.
• Despite success, AAV gene therapy faces challenges including host immune responses and potential genotoxicity from vector integration.
• Current preclinical models may not fully replicate human physiology, hindering the understanding of AAV vector behavior and safety.

Purpose of the Study:

• To review adeno-associated virus (AAV) gene therapy and its current limitations.
• To explore the potential of 3D organoids, microphysiological systems, and body-on-a-chip platforms as advanced preclinical models for AAV gene therapy.
• To discuss the application of these novel models in addressing critical questions about AAV biology and toxicity.

Main Methods:

• Review of existing literature on AAV gene therapy and preclinical models.
• Discussion of the capabilities of 3D organoids, microphysiological systems, and body-on-a-chip platforms.
• Presentation of case examples demonstrating the utility of these advanced models.

Main Results:

• 3D organoids, microphysiological systems, and body-on-a-chip platforms offer enhanced recapitulation of human physiology compared to traditional animal models.
• These advanced models can provide novel insights into AAV vector immunogenicity and genotoxicity.
• Successful applications demonstrate their power in answering complex questions in AAV gene therapy research.

Conclusions:

• Novel preclinical models like organoids and body-on-a-chip systems are essential for advancing AAV gene therapy.
• These models can help overcome current hurdles related to host immunity and genotoxicity.
• Adoption of these systems is critical for the safe and effective development of future gene therapies.