AAV Capsid Development
The ATHENA AAV capsid platform enables users to efficiently evaluate and evolve AAV serotypes or variants that are customized for specific therapeutic applications.
ATHENA Capsid Development Platforms
ATHENA platform includes three different sub-platform: ATHENA-I, ATHENA-II, ATHENA-III. By combining the three sub-platforms with AI, the ATHENA platform can efficiently identify, evolve and create the best AAV capsids for specific applications, potentially improving the effectiveness of gene therapy and reducing costs.
- ATHENA-I platform is known barcoded AAV capsid library, which is used to systematically evaluate different AAV serotypes or variants by using Barcode-Seq and NGS technology;
- >1000 AAV capsids;
- 1 capsid = 3 barcodes
- ATHENA-II platform is high complexity random peptide insertion AAV capsid library, which is designed to evolve novel AAV capsids with tissue-specific tropism.
- Any capsid, VR, insertion peptide
- Complexity>1e9
- ATHENA-III platform is a rational DNA shuffling AAV capsid library, which is used to create novel hybrid AAV capsids with improved transduction or other properties.
- Combine advantages of selected capsids
Creating Novel AAV Capsids with ATHENA Platform
AAV Products/Services Based on ATHENA Platform
Methods of AAV Capsid Engineering
- Directed Evolution: This technique generates large libraries of AAV capsid variants, selecting those with desirable properties through iterative screening. Capsid libraries are created using:
- Error-Prone PCR: Introducing random mutations into the AAV capsid gene.
- Insertional Mutagenesis: Adding peptides or sequences to specific capsid regions.
- DNA Shuffling: Recombining sequences from multiple AAV serotypes to produce chimeric capsids.
- Rational Design: Using detailed structural knowledge, researchers make targeted capsid modifications to enhance function. Specific changes like point mutations, insertions, or deletions in key regions improve interactions with receptors or immune components. For instance, altering surface loops (variable regions) can enhance tissue specificity.
- Peptide Display: Short peptides are inserted into surface-exposed capsid loops to create new binding sites, improving tissue targeting or receptor binding. This method designs AAV vectors that selectively target specific cells by leveraging peptide-receptor interactions.
- Chimeric Capsids: Combining capsid gene segments from different AAV serotypes creates chimeric capsids with the best traits of multiple serotypes. These capsids often show enhanced tropism, reduced immunogenicity, and improved transduction efficiency compared to the originals.