Approaches towards biomaterial-mediated gene editing for cancer immunotherapy

Gene therapies are transforming treatment modalities for many human diseases and disorders, including those in ophthalmology, oncology, and nephrology. To maximize the clinical efficacy and safety of these treatments, consideration of both delivery materials and cargos is critical. In consideration of the former, a large effort has been placed on transitioning away from potentially immunoreactive and toxic viral delivery mechanisms towards safer and highly tunable nonviral delivery mechanisms, including polymeric, lipid-based, and inorganic carriers. This change of paradigm does not come without obstacles, as efficient non-viral delivery is challenging, particularly to immune cells, and has yet to see clinical translation breakthroughs for gene editing. This mini-review describes notable examples of biomaterial-based gene delivery to immune cells, with emphasis on recent in vivo successes. In consideration of delivery cargos, clustered regularly interspaced palindromic repeat (CRISPR) technology is reviewed and its great promise in the field of immune cell gene editing is described. This mini-review describes how leading non-viral delivery materials and CRISPR technology can be integrated together to advance its clinical potential for therapeutic gene transfer to immune cells to treat cancer.