Recent advances in synthesis of modified oligonucleotides

Department of Biotechnology, CGO Complex, Lodhi Road, New Delhi-110 003, India Nucleic Acids Research Laboratory, Centre for Biochemical Technology, Mall Road, Delhi-110 007, India Manuscript received 26 April 1999, revised 31 August 1999, accepted 1 September 1999 With the advent of oligonucleotides as potential therapeutics, the search for modified analogs of nucleic acids having im­proved properties, such as increased stability against nucleases, improved cellular uptake and enhanced binding affinity to complementary nucleic acids with high specificity, has accelerated rapidly and has attracted considerable attention. Specific binding through natural base pairing has become increasingly important for the development of DNA based diagnostics as well as therapeutics in the form of antisense and antigene oligonucleotides. Modified DNA based oligonucleotides can affect the gene expression at the level of translation as well as transcription. The automation of oligonucleotide synthesis, the de­velopment of better coupling reagents as well as support system and efficient scale-ups have expanded the application of these molecules to diverse areas of fundamental as well as applied biological research. The modified molecules are expected to find answers to understanding, unveiling and utilizing the intricate methods of cell functioning at the molecular level and would provide applications in genetic engineering, gene therapy and cellular regulations in an array of conditions. In this review, the synthesis or the assembling of oligonucleotides modified at the backbone, or at the base, or at the sugar resi­dues, has been brought into sharp focus