VectorBuilder Inc. – provider of gene delivery solutions – has announced its plan to invest $30 million to build an ‘AAV Superbank’ for the research and drug discovery community. The company will develop a comprehensive collection of novel adeno-associated virus (AAV) capsids capable of targeting all the major tissues of therapeutic relevance, and deposit their sequences in the Superbank along with detailed biodistribution data. This bank will be made public, allowing free non-profit research use and license-based for-profit use.
Recombinant AAVs have become the most popular gene delivery vector for a variety of research and clinical applications in recent years, especially in gene therapy. The tropism of AAV, namely its ability to target specific tissues in the body, depends on the structure of the capsid protein that forms the outer shell of the virus.
There are currently over a dozen commonly used AAV capsid variants possessing different tropisms for different tissues, but this is far from covering all the major human tissues, let alone individual cell types within each tissue. Furthermore, even if a given AAV capsid displays tropism for a particular tissue, the targeting efficiency and specificity is often poor. As a result, large quantities of virus are often needed to achieve therapeutic efficacy, which can lead to significant toxicity and high manufacturing costs.
To address this issue, VectorBuilder has developed a highly effective AAV capsid screening platform that combines its innovative library construction technology with AI deep learning.
VectorBuilder’s chief scientist, Dr. Bruce Lahn, commented: “This platform allows us to efficiently survey a vast capsid sequence space rapidly and at a reasonable cost. Moreover, we can perform screening in non-human primates (NHPs), which ensures the best translatability to humans. This platform has already demonstrated its power in our internal R&D and contract research projects, where we have identified new capsids with dramatically improved targeting of some tissues. This includes capsids with orders of magnitude greater efficiency at crossing the brain-blood barrier, as well those specifically targeting cone and rod cells in the retina.”
“Our plan is to use our screening platform directly on NHPs to identify and validate a large panel of capsids that collectively target all the major tissues and important cell types with high efficiency and specificity, and we also plan to screen for capsids with low toxicity and immunogenicity to reduce side effects in gene therapy,” Dr. Lahn added. “The establishment of the AAV Superbank will likely take several years, but it is worth the effort, as it will bring great value to the burgeoning field of genetic medicine.”