Next-generation AAV vectors for clinical use: an ever-accelerating race

Area of Science:

• Biotechnology
• Molecular Biology
• Virology

Background:

• Adeno-associated virus (AAV) is a potent gene delivery platform for clinical applications.
• The viral capsid dictates host interaction, cell specificity, and immune response, making it a key target for modification.
• Engineering AAV capsids aims to enhance features for improved gene therapy efficacy.

Purpose of the Study:

• To introduce and discuss two novel strategies for accelerating Adeno-associated virus (AAV) evolution.
• To address challenges in developing high-throughput AAV capsid engineering.
• To facilitate the development of next-generation AAV vectors for clinical gene therapy.

Main Methods:

• Description of an ancestral Adeno-associated virus (AAV) sequence reconstruction approach (reverse genetics).
• Explanation of AAV genome barcoding technology for advancing genetic strategies.
• Discussion of how these methods complement forward genetics approaches.

Main Results:

• These strategies aim to overcome limitations in library quality, fidelity, and complexity for AAV engineering.
• Both ancestral sequence reconstruction and genome barcoding accelerate AAV evolution.
• These methods contribute to the development of superior synthetic AAV capsids.

Conclusions:

• Novel reverse genetics and genome barcoding strategies accelerate Adeno-associated virus (AAV) evolution.
• These approaches enhance the development of next-generation AAV vectors for gene therapy.
• Tailored acceleration of AAV evolution is crucial for advancing clinical applications.