In the past decade, AAV vector, have taken center stage as a gene delivery vehicle for the potential gene therapy for a number of human diseases. Nevertheless, challenges have become apparent, such as the need for high vector doses and the induction of anti-AAV immune responses that cause the loss of vector-transduced hepatocytes. The various serotypes and variants of AAV that have been described can transduce a wide array of cells. Yet, the limited diversity of natural AAV serotypes restricts the application of AAV gene therapy vectors to certain target tissues and associated diseases.
This fostered research focusing on development of next-generation AAV vectors capable of dealing with these hurdles. Capsid engineering is a promising strategy to significantly improve efficacy of the AAV vector system in clinical application. Reduction in vector dose will further improve vector safety, lower the risk of host immune responses and the cost of manufacturing. Capsid engineering is also expected to result in AAV vectors applicable to patients with preexisting immunity toward natural AAV serotypes.
At AAVnerGene, we developed ATHENA AAV screening platforms, which allow users to quickly evaluate, evolve, and create AAV serotypes or variants tailored for specific therapeutic applications.
ATHENA AAV Capsid Screening Platform
ATHENA platform includes three different sub-platform:
AAV Capsid Libraries(I) are AAV products created using ATHENA I platform. In the AAV Capsid Libraries(I), each capsid variant was assigned to three different DNA barcodes. By comparing DNA or RNA levels of the reporter gene with NGS targeting the DNA barcodes, researchers can determine which AAV capsid variant is the most efficient for their specific application.
AAVnerGene provides common and tissue-specific AAV capsid libraries(I). Common one includes 16 widely used AAV serotypes. Tissue-specific libraries have additional 9 selected tissue-targeting capsids. We also provide custom library services, users can provide their own reporter systems and add any tissues specific capsids into the kits.
ATHENA II platform is designed to evolve novel AAV capsid with tissue-specific tropism from high complexity random peptide insert library.
AAV Capsid Libraries(II) are random peptide insert library build on our ATHENA II platform. In the premade AAV Capsid library(II), CAP gene with random peptide are driven by a CAG/P40 hybrid promoter. P40 promoter was used to drive CAP expression during AAV production. CAG promoter is used to express CAP in targeting cells or tissues. The random peptides themselves can serve as barcodes for enrichment analysis.
AAVnerGene provides AAV Capsid libraries(II) with different serotypes, insert variable regions and insert random peptide lengths. Each library has complexity over one Billion. We aslo provide custom libraries construction, production and evolution services
- ATHENA III is a rational DNA shuffling library used to create novel hybrid AAV capsids.
- Our ATHENA III are created based on ATHENA I NHP selection results. Currently, this system only for collaboration. For more information, please contact us.
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.