Recent Advances in Lipid Nanoparticle-Mediated mRN A Therapy

摘要

All cells function by an intricate mechanism that converts information stored as nucleic acid sequences (DNA) into messages (messenger RNA) for translation into functional products (protein). Endogenous checks and balances exist within this information flow, which can be leveraged as therapies to treat diseases closer to their genetic origin. The significant health opportunities of gene therapies are evident in the growing number of synthetic drugs, as well as modified viral delivery systems, which have recently been approved or entered clinical development. Many of these products seek to decrease the presence of disease-causing proteins, counteract the effects of defective genes or introduce exogenous materials. Compared to conventional treatments designed to induce transient therapeutic effects, nucleic acid-based drugs can achieve more specific, long-lasting or curative effects. However, therapeutics based on unmodified nucleic acids display poor pharmacokinetics and biodistribution, are rapidly broken down in circulation, and can trigger immune responses. They also exhibit unfavorable physicochemical properties that prevent diffusion across the plasma membrane of target cells. Accordingly, the entry of nucleic-acid products into clinical development is largely dependent upon delivery technologies and applied chemistry that enable functionality.