Recently, Prof. Hanmei Xu's team from Jiangsu Engineering Research Center for Synthetic Peptide Drug Discovery and Evaluation, China Pharmaceutical University, published a review article entitled “Nucleic acid drugs: recent progress and future perspectives” in Signal Transduction and Targeted Therapy (IF=40.8). Xiaoyi Sun, Sarra Setrerrahmane, Chencheng Li, and Jialiang Hu are the lead authors of the paper, and Prof. Hanmei Xu is the corresponding author. China Pharmaceutical University is the first corresponding organization of the paper.
Nucleic acid drugs are a class of gene therapeutic compounds based on DNA, RNA or synthetic oligonucleotide analogs, which have the advantages of significant therapeutic efficacy and short development cycle. In recent years, the base modification of mRNA as well as the gene regulatory role of miRNA have been awarded the Nobel Prize for Physiology or Medicine one after another, and the field of nucleic acid drugs is becoming the hot spot of the current stage of the market of clinical medication and new drug development. Researchers have developed nucleic acid drugs by taking advantage of the translational or regulatory functions of endogenous nucleic acids, which can achieve long-lasting therapeutic efficacy by means of gene inhibition, replacement, and editing, etc. At the same time, a large number of studies have also shown that nucleic acid drugs have great potential for clinical application in the treatment of antiviral, antitumor, and neuromuscular diseases.
In this article, the authors firstly review the development history, classification and mechanism of action of nucleic acid drugs, and summarize the general difficulties faced during the development of nucleic acid drugs. Based on this, the authors briefly outline the delivery strategies of nucleic acid drug modification (chemical modification and delivery vehicles), with a focus on the progress of the research on peptides as novel nucleic acid drug delivery vehicles, and introduce different kinds of peptides for nucleic acid drug delivery, and introduce different kinds of peptides to assist the delivery of nucleic acid drugs. It focuses on the progress of peptides as novel nucleic acid drug delivery vehicles, introduces different types of peptides that assist in nucleic acid drug delivery and reviews current strategies for nucleic acid drug delivery, including peptide-nucleic acid couplings, peptide nanoparticles, and composite delivery systems formed by combining peptides with other delivery vectors, and concludes with a summary of the progress of nucleic acid drugs in clinical applications, as well as their limitations and potential future applications as candidates for gene therapy. The development of nucleic acid drugs is a systematic effort due to the complexity of nucleic acid types, sizes, and mechanisms of action; therefore, the organic combination of specific therapeutic nucleic acid molecules, targeted modifications, and functionalized delivery vectors may hold the key to realizing personalized nucleic acid therapies, which are expected to address the currently unmet clinical needs.
Link to full article: https://doi.org/10.1038/s41392-024-02035-4
Clinical applications of nucleic acid drugs. A variety of nucleic acid drugs have been used in the treatment of rare genetic diseases, cancer, ophthalmic diseases, cardiovascular diseases and infectious diseases, and have demonstrated remarkable therapeutic effects.
