Debugging the genetic code: non-viral in vivo delivery of therapeutic genome editing technologies

摘要

Efforts to precisely correct genomic mutations that underlie hereditary diseases for therapeutic benefit have advanced alongside the emergence and improvement of genome engineering technologies. These methods can be divided into two main classes: active nucleasebased platforms including the popular CRISPR/Cas9 system and oligo/polynucleotide strategies including triplex-forming oligonucleotides (TFOs), such as peptide nucleic acids (PNAs). These technologies have been successful in cell culture and in animals, but important challenges remain before these tools can be translated into the clinic; they must be effectively delivered to and taken up by specific cell types of interest, achieve correction levels in target cells that significantly ameliorate the disease phenotype, and demonstrate minimal off-target and toxicity effects. Here we review and compare the current strategies and non-viral delivery methods, mainly lipid and polymeric vehicles, proposed for genome editing of inherited disorders with a focus on in vivo delivery and efficacy. While the path to a safe and effective medical treatment may be arduous, the future outlook of therapeutic genome editing remains promising as long as precise technologies can be combined with efficient delivery.