Gene therapy has been in discussion since 1972, but its translation to clinical practice has been a slow and challenging process . Aside from its steep cost at 1.6 million dollars per patient , current gene modification methods are ethically questionable, short-lived, and can result in harmful immune responses . More serious complications can also arise due to off-target effects, such as germ line mutations or activation/alteration of the incorrect portion of the genome . Although current in vivo gene therapies are ineffective and controversial, a novel peptide-based delivery method could drastically improve future studies.
While many researchers boast the benefits of gene therapy for treating recessive genetic disorders (e.g., sickle cell anemia, cystic fibrosis), very few therapies have seen success in clinical trials, in part due to the choice of vector . Since viruses (and viral vectors) have evolved over millions of years to deliver DNA and RNA into a foreign host, they are extremely effective at delivering genetic material to a target cell in the context of gene therapy . However, viral vectors must first get past the immune system. Immunity to viral capsules is one of the biggest challenges in gene therapy to date, as commonly used vectors are derived from harmless viruses circulating in humans . Additionally, an undesired immune response could occur and be fatal for immunocompromised individuals .
On the other end of the spectrum, non-viral vectors for in vivo gene therapy greatly reduce the risk of unwanted immune responses, but with the trade-off of lower delivery efficiency . Although advances in specificity, efficiency, and gene expression duration have led to their increased use in clinical trials, non-viral vector properties can still be improved . As a solution to this translational challenge, Allen et al. have proposed a peptide-based delivery method of Cre recombinase for in vivo gene therapy .