Viral and non-viral delivery methods that introduce foreign genetic material in cells are widely used in cell therapy applications. While effective in certain cell types, current techniques often are detrimental to cell viability and cell potency, leave genetic footprints, and pose important safety and regulatory concerns. One promising avenue to bypass the use of foreign DNA and virus in cell therapy consists on the direct delivery of active proteins. However, the poor efficiency of current protein delivery methods, mainly caused by endosomal entrapment, slowed down the transfer of this approach toward cell therapy.
In order to fulfill a need for an efficient and appropriate protein delivery method for ex vivo cell therapy and in vivo administration through local injections, we developed a proprietary peptide technology that enables robust entry of fluorescent proteins, antibodies, peptides and CRISPR nucleases in cells by a simple co-incubation. Initially based on natural domains, these carrier peptides that combine a cell penetration function with an endosomal leakage activity are now rationally designed and optimized for their ability to deliver proteins in hard-to-transfect cells, including Natural Killer cells and primary airway epithelia cells. The flexibility, efficiency and simplicity of this peptide-based technology, the Feldan Shuttle, open new avenues for ex vivo and in vivo therapies.