Gene therapy is a cutting-edge medical treatment that involves modifying or manipulating an individual's genes to treat or cure diseases. It may involve replacement of a faulty gene with a healthy one, inactivation of an overactive or defective gene, or introduction of new gene to promote healing. Enterprise BX has an active Gene Therapy Program directed towards the Oncology Market. The Oncology market is expected to be $394 Billion by 2027. It has grown at the rate of 12.1% since 2021. Gene Therapy directed towards Oncology is likely to capture significant portion of the market due to its curative potential and fewer side effects.

Targeting Pancreatic Cancer Using Viral Vectors and Nanoparticles as Delivery Vehicles:

WWOX protein (WW domain-containing oxidoreductase) plays several important roles in  humans. These roles include genomic stability, apoptosis and tumor suppression. It interacts through its WW-domain (a 20-22 amino acid domain flanked by two tryptophans) with proline rich domain of target proteins. It has been shown that the targeted deletion of murine WWOX promotes Ras oncogene and pancreatic carcinogenesis. Our preliminary studies using our proprietary in vitro model of pancreatic organoids have shown that we can deliver WWOX mRNA specifically to pancreatic cancer cells using a combination of viral vectors and proprietary biodegradable, nanoparticles. Additionally, our in vitro model allows screening for small molecules for treatment of pancreatic cancer and further enhances the chances of success for our Gene Therapy via combination therapy approaches.

Targeting Cancer through CRISPR/Cas9 Technology:

CRISPR/Cas9 is a molecular scissor for DNA. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a sequence of DNA found in bacteria. Cas9 (CRISPR-associated protein 9) is an enzyme that cuts DNA at specific locations. The technology is used for Gene Editing. The Cas9 is directed to the specific site where DNA is to be cut using a small guide RNA sequence. CRISPR/Cas9 can be used to precisely edit genes that are involved in cancer development. By knocking out oncogenes (cancer-causing genes) or correcting mutations in tumor suppressor genes, several cancers can be treated. Enterprise BX has recently embarked upon a program based on this concept. The TP53 protein is a tumor suppressor that promotes cell cycle arrest, DNA repair, and apoptosis. The TP53 gene is defective in almost 50% of pancreatic cancers. Correction of mutations or insertion of functional gene copies should inhibit pancreatic cancer. The KRAS promotes cell proliferation and survival in 30% of pancreatic and 40% of colorectal cancers.

Similarly, the EGFR promotes cell proliferation, survival, and migration. Disruption of these oncogenes should help in treating pancreatic and colorectal cancers.

Enterprise BX will conduct comprehensive genomic analyses to identify key oncogenes and tumor suppressor genes involved in various cancers. We will also utilize bioinformatics tools to predict potential off-target effects and ensure specificity. Using CRISPR/Cas9 technology we will disrupt the selected oncogenes and repair suppressor genes. We will then validate our modified genes in cell-based models and then test the selected candidates in animal models. Systematic preclinical and clinical studies will then follow. We expect to try our first candidate in

clinical trials in about 3 years.