603. Feldan Shuttle - Advanced Protein Delivery Technology for Cell Therapy

Abstract

Methods for maximizing the therapeutic value of human cells often involve the transfer of genetic material and use of viruses, both raising important safety and economical concerns. One promising solution to improve cell therapy processes consists on the direct delivery of active proteins into human cells. Regenerative medicine studies established powerful proofs of concept using delivery of transcription factors for cell reprogramming and differentiation; however, the lack of efficiency of current protein delivery methods slowed down the transfer of these methods toward human clinical researches. In the last years, the CRISPR/Cas9 revolution brought forward the possibility of using diverse transfection approaches to deliver Cas9 protein complexed with guide RNA, a method yielding interesting results with cationic lipid agents and electroporation systems. In a human therapy context, lipidic agents are generally not suitable because of their high cellular toxicity. As for electroporation, few systems have been approved for cell therapy; in addition, this process represents a serious concern because of its high cost, inconsistency, associated cell mortality and the fact that some cells are simply refractory to electroporation. In all, these characteristics accentuate the need for a protein delivery process suitable for human cell therapy. In order to efficiently use transcription factors, Cas9 or any other intracellular proteins in cell therapy, Feldan Therapeutics is developing a protein delivery agent, the Feldan Shuttle, explicitly designed for cell therapy. Feldan Shuttle is entirely protein-based, thus allowing cells to naturally degrade it and the delivered protein after their active use. With this novel method, Feldan Therapeutics successfully delivered fluorescent proteins as well as functionally active transcription factors and Cas9/RNA complex with high efficiency and low toxicity into multiple cell lines and human primary cells. With this new technology, Feldan Therapeutics offers an innovative method designed to efficiently and safely deliver native proteins for cell therapy applications.