RESUMO
Small nucleic acid drugs, composed of nucleotides, represent a novel class of pharmaceuticals that differ significantly from conventional small molecule and antibody-based therapeutics. These agents function by selectively targeting specific genes or their corresponding messenger RNAs (mRNAs), further modulating gene expression and regulating translation-related processes. Prominent examples within this category include antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), microRNAs (miRNAs), and aptamers. The emergence of small nucleic acid drugs as a focal point in contemporary biopharmaceutical research is attributed to their remarkable specificity, facile design, abbreviated development cycles, expansive target spectrum, and prolonged activity. Overcoming challenges such as poor stability, immunogenicity, and permeability issues have been addressed through the integration of chemical modifications and the development of drug delivery systems. This review provides an overview of the current status and prospective trends in small nucleic acid drug development. Commencing with a historical context, we introduce the primary classifications and mechanisms of small nucleic acid drugs. Subsequently, we delve into the advantages of the U.S. Food and Drug Administration (FDA) approved drugs and mainly discuss the challenges encountered during their development. Apart from researching chemical modification and delivery system that efficiently deliver and enrich small nucleic acid drugs to target tissues, promoting endosomal escape is a critical scientific question and important research direction in siRNA drug development. Future directions in this field will prioritize addressing these challenges to facilitate the clinical transformation of small nucleic acid drugs.
RESUMO
OBJECTIVE To know about the development trend of small nucleic acid drugs in the world ，to provide reference for the research and development of small nucleic acid drug in China. METHODS By searching the academic literature and patents related to small nucleic acid drugs through the Web of Science literature database and PatSnap patent database from Jan. 1980 to Dec. 2021，research and development situation of small nucleic acid drugs were revealed comprehensively by analyzing research enthusiasm，R&D countries ，R&D institutions and technical topics of small nucleic acid drugs. RESULTS & CONCLUSIONS A total of 59 819 documents and 37 645 patent groups were included. The global trend of small nucleic acid drug literature publication and patent application could be divided into three stages. From 2003 to 2021，the research enthusiasm for small nucleic acid drugs continued to increase. The United States ，China，Japan and Germany were the main research and development countries for small nucleic acid drugs. The number of document publications （25 703，15 927 papers）and patent applications （14 240、8 937 groups） in the United States and China were ahead of other countries ，and the research and development activities were relatively strong. Moreover，the number of document publications and patent applications in China in this field had grown rapidly in recent years. The R&D institution with the largest number of publications was the University of California （2 499 papers），the R&D institution with the largest number of patent applications was the American Ionis Corporation （1 378 groups），and the Chinese Academy of Sciences （1 580 papers）had been shortlisted among the top 10 document producing institutions in the world. However ，our country ’s research and development in this field are mostly based on basic research ，and the research on industrial application is slightly insufficient. The research focus in the field of small nucleic acid drugs mainly focuses on nucleic acid sequences and their modification and improvement and drug loading technology. RNA interference technology has gradually become a hot technology for small nucleic acid drugs.