Polymeric Vehicles for Nucleic Acid Delivery
In contrast to small molecule drugs that transiently target proteins rather than address the underlying cause of genetic diseases, gene therapeutics (anti-sense oligonucleotides, mRNA, pDNA, siRNA) modulate gene expression to achieve long-lived therapeutic effects. Additionally, genome editing technologies such as CRISPR/Cas9, prime editing, and base editing offer the possibility of permanent cures for genetic disorders. Therapeutic nucleic acids augment, delete or otherwise modify defective gene sequences, and are steadily winning approval for clinical use from regulatory agencies. Delivery vehicles must protect nucleic acids from degradation, minimize the risk of activating the immune system, and ultimately deliver these payloads to target cells safely and efficiently. The bulk of clinically approved gene therapeutics rely on engineered viral vectors that encode the requisite DNA sequences, but viral delivery is confronted with issues of cost, manufacturability, and safety. Lipid nanoparticles and physical methods of gene delivery have been developed but they are ill-suited for use in rugged environments where cold storage and specialized equipment may be unavailable.