The most common form of gene therapy delivers a functional copy of the gene of interest to the patients’ cells to replace or supplement the activity of the mutated gene. To ensure the functional copy of the gene is delivered successfully, the gene is inserted into a vector that can enter the cell without harming it. At AGTC we use the non-toxic adeno-associated virus (AAV) to deliver the gene of interest. AAV is a safe virus that has never been known to cause disease, and has been approved for use in human clinical trials by U.S. and European regulatory agencies.
The AAV vector has a protective protein shell called a capsid. The capsid is the primary interface between the virus containing the functional copy of the gene of interest and the target cells. AAV capsid structures can have distinct features that improve the efficiency and specificity of delivery of the functional gene into cells. Capsids can be tailored to certain cell types that are affected by a particular condition to ensure better entry into those cells. The capsid structure can also play a role in the production and yield of AAV. Capsid modifications can facilitate process development, vector stability and storage. At AGTC we design and select the best capsids to minimize potentially adverse responses and ensure successful delivery of the functional gene.
A promoter is a region of DNA that drives gene expression once the gene is delivered to the appropriate cell. There are two types of promoters: those that activate only in specific cell types (called tissue-specific promoters) and those that allow for gene expression in a wider variety of cell types (called ubiquitous promoters). At AGTC we select promoters based on the characteristics required for each condition. Some conditions are best served with tissue-specific promoters to avoid expression of proteins in cells where it might interfere with function. Other conditions are best served with ubiquitous promoters to allow for maximal protein production.
At AGTC we focus on selecting the best promoter for each indication to ensure the most effective and specific gene expression possible.
A gene cassette is an element that contains the instructions needed to ensure protein expression once the gene is introduced inside the cell.
Successful gene expression depends on the proper design of the gene cassette. At AGTC we use novel gene cassettes that have been optimized for use in humans by a variety of methods. Our gene cassettes are screened for safety and efficacy in appropriate animal models to maximize their potential prior to human clinical trials.
AGTC is developing novel formulations for gene therapy. These formulations have shown promise in their ability to increase the concentration and stability of the gene therapy while reducing unwanted effects for the patient. Our proprietary formulation allows us to reach therapeutic doses at lower volumes which enhances the ability of the therapy to benefit patients.
Manufacturing & Characterization
AAV vectors have broad potential to treat a variety of genetic conditions. Our proprietary manufacturing system allows us to handle large volumes, reduce cost, and increase potency and purity of gene therapy treatments. We combine the consistent high yields from our manufacturing system with advanced characterization methods to accelerate the development of gene therapies into human clinical trials. This production and characterization system has been positively reviewed by the U.S. Food & Drug Administration (FDA) and European Medicines Agency (EMA) for use in human clinical trials and has been successfully transferred to multiple vendors and partners.
AGTC’s most advanced ophthalmic product candidates in XLRP and ACHM are currently delivered via subretinal injection. Based on studies we have conducted as well as other publicly available data, we believe this delivery technique optimizes overall patient outcomes.
Subretinal administration is a minimally invasive surgical procedure which involves delivery of the AAV vector underneath the retina. Although this delivery method is a more direct way to introduce the vector to the targeted cells, it requires general anesthesia and a refined surgical technique aimed at maximizing potential benefit while minimizing risks.
AGTC intends to evaluate additional, novel capsids and delivery techniques for the earlier stage product candidates in its pipeline with an objective of enabling more clinicians to administer such candidates treat larger patient populations.