Recent advances in synthesis of modified oligonucleotides

With the advent of oligonucleotides as potential therapeutics, the search f or modified analogs of nucleic acids having improved properties, such as in creased 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 bind ing 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 oligonucleotid es can affect the gene expression at the level of translation as well as tr anscription. The automation of oligonucleotide synthesis, the development o f better coupling reagents as well as support system and efficient scale-up s have expanded the application of these molecules to diverse areas of fund amental as well as applied biological research. The modified molecules are expected to find answers to understanding, unveiling and utilizing the intr icate 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 sug ar residues, has been brought into sharp focus.