An Integrated Approach to Engineering DNA Therapeutics that Achieves Long-Term Efficacy
Many rare genetic disorders are based on the mutation of a single gene (“monogenic” disorders). Agilis’ transformative approach to treating these types of rare disorders is based on delivering a corrected copy of a naturally occurring gene directly to targeted cells. Once inside the cell, the cell’s machinery uses the therapeutic DNA to produce the functional protein that the defective DNA could not, thus correcting the disease pathology by restoring normal protein production and function in cells. The corrective DNA is transported to the appropriate cells by a specially engineered vector that enables precise targeting and delivery of the DNA to the targeted cells.
Our innovative DNA therapeutics combine proprietary gene construct technologies, optimized gene delivery vectors, and proprietary techniques and know-how to achieve highly potent, targeted, and safe gene therapies designed to achieve long-term efficacy in patients. Our integrated strategy is designed to accelerate product development and clinical trials to rapidly provide therapeutic solutions that deliver the best possible outcomes for patients in dire need of treatment.
Our approach involves:
- Understanding the underlying genetic mechanism of a rare CNS disease;
- Engineering novel, best-in-class DNA constructs that carry corrective DNA tailored to be potent and effective in specific CNS cell types;
- Optimizing gene expression and performance through a rigorous design-build-test process and deep insights into gene regulation;
- Integrating precision-targeted vectors to guide the DNA therapeutic to the right cells; and
- Identifying and developing powerful drug delivery technologies for precise administration of the corrective DNA to the CNS.
We leverage synergistic technology platforms by actively seeking, investing in, and integrating best-in-class enabling technologies, knowledge, and strategic partnerships that will support the rapid advancement of our DNA therapeutics.
Enhanced molecular insight into the rare diseases we address:
Our team has an intimate understanding of gene expression in the specific CNS diseases or disorders we address. We make significant investments in understanding how gene expression is regulated in the disease cell types targeted, and in methods for optimizing gene effectiveness in the course of treatment.
Best-in-class DNA constructs:
Agilis’ DNA therapeutics are based on wild-type (i.e., naturally occurring) genes that have been engineered with finely tuned regulatory elements to achieve the optimal level of expression for the disease. Using an industrialized, data-driven process, we rapidly and rigorously design, test, analyze, and screen broad arrays of purpose-built gene constructs to identify and select candidates that have optimal performance characteristics for a specific CNS disease application.
Powerful targeting technologies for safe and efficient delivery of DNA to CNS-specific cells:
Agilis uses best-in-class AAV (adeno-associated virus) vector systems for targeted administration of our therapeutic DNA to specific CNS cell types at the optimal time, location, and concentration to facilitate long-term therapeutic benefit. Extensive studies, including in CNS disease targets, have established AAV vector systems as the safest and most efficient vectors for delivery of functional DNA to specific targeted cells and tissues. Advantages of AAV vectors include:
- Achievement of stable, long-term protein expression;
- Non-integration into DNA (thereby avoiding mutations and potential cancers); and
- Ability to transfer DNA into the non-dividing cells of the CNS.
By developing our proprietary DNA therapeutics, Agilis is building an intellectual property portfolio through the use of patents, trademarks, copyrights, trade secrets, and other proprietary or regulatory means to protect our products. We are constantly pursuing state-of-the-art solutions and investigating innovative ways to augment gene expression in cells. Our deep understanding of how genes are activated and transcribed, and how genetic information is translated into functional proteins, enables us to design proprietary, finely-tuned genetic constructs based on naturally occurring genes that power our target indications, and for which we seek broad intellectual property protection. Our novel therapeutic approach is augmented by an ever-expanding knowledge base that affords unique insights into the treatment of rare genetic disorders.