Nucleic Acid Conjugates: Unlocking Therapeutic Potential

被引：0
作者：
Kashyap, Disha [1 ]
Booth, Michael J. [1 ,2 ]
机构：
[1] Univ Oxford, Dept Chem, Oxford OX1 3TA, England
[2] UCL, Dept Chem, London WC1H 0AJ, England
来源：
ACS BIO & MED CHEM AU | 2024年 / 5卷 / 01期
基金：
英国工程与自然科学研究理事会; 英国惠康基金;
关键词：
Nucleic acid therapeutics; antisense oligonucleotides; small interfering RNA; aptamers; splice switching; gene knockdown; bioconjugation; cell delivery; cell targeting; targeted activation; ANTISENSE OLIGONUCLEOTIDES; INTRACELLULAR DELIVERY; MORPHOLINO OLIGOMERS; RNA INTERFERENCE; IN-VITRO; GENE; SIRNA; ANALOGS; PHARMACOKINETICS; APTAMER;
D O I：
10.1021/acsbiomedchemau.4c00092
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Nucleic acids have emerged as a powerful class of therapeutics. Through simple base pair complementarity, nucleic acids allow the targeting of a variety of pathologically relevant proteins and RNA molecules. However, despite the preliminary successes of nucleic acids as drugs in the clinic, limited biodistribution, inadequate delivery mechanisms, and target engagement remain key challenges in the field. A key area of research has been the chemical optimization of nucleic acid backbones to significantly enhance their "drug-like" properties. Alternatively, this review focuses on the next generation of nucleic acid chemical modifications: covalent biochemical conjugates. These conjugates are being applied to improve the delivery, functionality, and targeting. Exploiting research on heterobifunctionals, such as PROTACs, RIBOTACs, molecular glues, etc., has the potential to dramatically expand nucleic acid drug functionality and target engagement capabilities. Such next-generation chemistry-based enhancements have the potential to unlock nucleic acids as effective and versatile therapeutic agents.
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页码：3 / 15
页数：13
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