hC Bioscience’s Preclinical Study Shows Promise for tRNA-Based Cancer Therapy

The Data was Presented at The 13th International Symposium of Aminoacyl-tRNA Synthetases (AARS2023)

hC Bioscience announced its tRNA-based therapy demonstrated proof-of-concept in an in vivo model of metastatic colorectal cancer with 75% tumor growth inhibition. This is the first report of a tRNA-based therapeutic showing feasibility in an in vivo cancer model, marking a significant milestone for tRNA-based therapies. The data showed that tRNA, engineered by hC Bioscience, can recognize and repair disease-causing nonsense mutations (premature stop codons) and produce functional, full-length tumor suppressor proteins. Because nonsense mutations drive an estimated 10-15% of cancers, tRNA-based therapy represents a potential new modality for the treatment of cancer.

The study tested two of hC Bioscience’s engineered tRNA candidates in several in vitro and in vivo models. The research specifically evaluated, among other measures, the impact tRNA had on mutated APC protein, which is associated with the growth of colorectal tumors cells. Key findings include the following:

• Engineered tRNA induced dose-dependent cytotoxicity in colorectal cancer cell lines in vitro
• Engineered tRNA was successfully delivered systemically using lipid nanoparticles to tumors in vivo
• On average over 75% growth inhibition of colorectal tumor (LoVo) in vivo
• Full-length synthesis of the APC tumor suppressor protein was restored in vivo and confirmed with immunohistochemistry on tumor tissues
• Inhibition of beta catenin in vivo.

“We reported in vivo data for the first time that clearly show the potential of engineered tRNA to restore tumor suppressor genes which produce the body’s natural tumor-fighting proteins,” said Leslie Williams, Co-Founder, President and CEO of hC Bioscience. “This strengthens our commitment to advancing our initial candidates toward an IND. In parallel, we continue to broaden our understanding of the molecular basis of tRNA and explore therapeutic areas beyond our initial indications as we optimize delivery for additional organs and tissues.”

The presentation, titled Anticodon engineered tRNA rescues expression of tumor suppressor proteins, resulting in growth inhibition of metastatic colorectal cancer models in vivo, was presented by Suchul Jang, Ph.D., Director of In Vivo Pharmacology at hC Bioscience, at The 13th International Symposium of Aminoacyl-tRNA Synthetases (AARS2023).