When used for therapy, cells are often modified through the introduction of exogenous molecules in their cytosol, a process called transfection. While a wide variety of transfection technologies have been developed, viral vectors currently hold a quasi-monopoly when it comes to therapeutic cell production. However, the use of viral vectors also comes with safety, productivity and financial limitations hampering the mass distribution of innovative and highly potent cell therapy products. As an alternative to viral vectors, physical transfection technologies, with electroporation at their forefront, emerged as promising alternatives enabling high throughput cell transfection. However, physical transfection, and electroporation in particular, typically show a highly cytotoxic profile decreasing the efficiency of the manufacturing procedure, affecting the therapeutic potency of the final cell product, and therefore limiting their use in the clinical setting.

After more than one decade of research and development on a novel physical transfection modality termed photoporation, the Braeckmans lab (Ghent University, Belgium) recently developed photothermal electrospun nanofibers (PEN) enabling harnessing the full potential of photoporation for therapeutic cell engineering. This novel technology exploits the interaction of nanosentisizers -embedded within a nanofiber substrate- with a laser light to gently induce pores in the cell membrane, thereby efficiently enabling transfection. In comparison to the state-of-the-art technologies, PEN photoporation simultaneously solves the safety and productivity limitations associated with viral vectors, and the toxicity limitations associated with electroporation.

Whereas PEN photoporation comes with important advantages making it amenable to therapeutic cell manufacturing, this technology has not been evaluated yet for the delivery of nucleic acids (mRNA and DNA) to stem cells. Optimizing photoporation for minimally perturbative delivery of large nucleic acids to e.g. iPSCs would, however, simultaneously open a myriad of opportunities to produce high-quality cell therapy products retaining their full therapeutic potency while enhancing cost-effectiveness relative to the currently available cell therapies. Consequently, further developing the PEN photoporation platform for cellular transfection with a wide array of effector molecules is one of the core objectives of the NOVISTEM project.

Originally published in Xiong et al., Photothermal nanofibers enable safe engineering of therapeutic cells, Nature Nanotechnology, 2021.