Temsamani J, Guinot P
Hybridon Europe, Paris, France.
Biotechnol Appl Biochem. 1997 Oct;26(2):65-71.
The use of antisense oligonucleotides as therapeutic agents has heralded a new field of genetic pharmacology. Oligonucleotides are relatively easy to design and display increased affinity and selectivity for their nucleic acid targets compared with traditional drugs. However, the development of antisense therapy has not been as simple as was first believed; many critical issues had to be addressed. The first generation of oligonucleotides investigated as drug candidates were phosphorothioate oligonucleotides. Several animal experiments have provided evidence that antisense oligonucleotides can inhibit gene expression of disease-associated proteins. These promising studies led to the advancement of these compounds into clinical trials in such diverse fields as infectious diseases, cancer and inflammation. The insights gained through ongoing clinical trials has opened the pathway to the design of second-generation oligonucleotides which have an improved safety profile and efficacy.
将反义寡核苷酸用作治疗剂开创了基因药理学的新领域。与传统药物相比，寡核苷酸相对易于设计，并且对其核酸靶点表现出更高的亲和力和选择性。然而，反义疗法的发展并不像最初认为的那么简单；必须解决许多关键问题。作为候选药物研究的第一代寡核苷酸是硫代磷酸寡核苷酸。多项动物实验已证明反义寡核苷酸可抑制疾病相关蛋白的基因表达。这些前景广阔的研究促使这些化合物在传染病、癌症和炎症等不同领域进入临床试验。通过正在进行的临床试验获得的见解为第二代寡核苷酸的设计开辟了道路，第二代寡核苷酸具有更好的安全性和疗效。
