Antisense therapy for cancer

Autor: F.E Cotter
Rok vydání: 2003
Předmět:
Zdroj: European Journal of Cancer Supplements. 1(2):19-27
ISSN: 1359-6349
DOI: 10.1016/s1359-6349(03)00011-9
Popis: Antisense oligonucleotides (AO) are short (typically 13–20 bases in length) sequences of single-stranded DNA or RNA complementary to expressed genes and are chemically modified to protect them from enzymatic breakdown. They are designed to hybridise by Watson– Crick base pairing with mRNA transcripts encoding proteins of interest and in this way ‘silence’ the expression of that particular gene and subsequently its protein product. The earliest attempt to inhibit gene expression using AO was reported in 1978. The Rous sarcoma virus was downregulated when exposed to a 13-base oligonucleotide complementary to the 30reiterated terminal sequences in a chick embryo fibroblast. Technology was developed in the early 1980s for automated synthesis of oligonucleotides with appropriate modifications of the backbones to protect against nuclease digestion and breakdown and greatly prolonging the duration of effect. With the great economy of scale, it has opened up the prospect of harnessing ‘gene silencing’, by synthetic oligonucleotides as a therapeutic tool for cancer. However, during the development of AO therapy, there have been a number of design and development problems to overcome.
Databáze: OpenAIRE