ADENO-ASSOCIATED VIRAL VECTORS AND USES THEREOF

Smart overview of the Invention

The patent application discusses the development and use of adeno-associated viral (AAV) vectors for cell transduction. These vectors are designed to enhance gene therapy applications by improving the efficiency and specificity with which they target cells. The invention addresses the challenge of engineering AAV capsids that can effectively transduce specific cell types while maintaining high production yields. This is particularly relevant for treating diseases that affect organs such as the central nervous system, liver, and heart.

Government Support and Sequence Listing

The research leading to this invention was supported by several grants from the National Institutes of Health, indicating that the government holds certain rights to it. Additionally, the application includes a Sequence Listing submitted in XML format, which is crucial for understanding the genetic sequences involved in these AAV vectors. This listing is a comprehensive document detailing specific sequences used in the invention.

Background and Challenges

A major challenge in developing AAV vectors is balancing multiple traits such as high production yield and efficient targeting of specific cell types. Traditional methods involve screening large libraries of peptide-modified capsids to find candidates with desired properties. However, optimizing these capsids for multiple traits remains difficult due to the vastness of protein sequence space. This often results in lengthy and resource-intensive development processes that may not yield optimal results.

Key Features of the Invention

The invention introduces AAV capsid polypeptides with inserted peptides containing specific amino acid sequences, which improve their functionality. These sequences are selected from a list provided in the patent, each contributing to enhanced traits such as transduction efficiency and production fitness. The application also details methods for screening these capsid libraries to identify those with desirable traits in various cell types and organs.

Applications and Benefits

The improved AAV vectors have potential applications across a range of medical fields, including gene therapy for neurological disorders, liver diseases, and cardiovascular conditions. By increasing transduction efficiency and production fitness, these vectors can more effectively deliver therapeutic genes to target cells. The invention also offers methods for creating viral particles with enhanced biodistribution, ensuring that therapeutic effects are achieved across different species and organ systems.