TAILIEUCHUNG - Báo cáo Y học: Optimizing the delivery systems of chimeric RNA . DNA oligonucleotides Beyond general oligonucleotide transfer

Special oligonucleotides for targeted gene correction have attracted increasing attention recently, one of which is the chimericRNAÆDNAoligonucleotide (RDO) system. RDOs for targeted gene correction were first designed in 1996, and are typically 68 nucleotides in length including continuous RNA andDNA sequences (RNA is 2¢-O-methyl-modified). | Eur. J. Biochem. 269 5753-5758 2002 FEBS 2002 doi REVIEW ARTICLE Optimizing the delivery systems of chimeric RNA DNA oligonucleotides Beyond general oligonucleotide transfer Li Liang De-Pei Liu and Chih-Chuan Liang National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Peking Union Medical College Beijing People s Republic of China Special oligonucleotides for targeted gene correction have attracted increasing attention recently one of which is the chimeric RNA-DNA oligonucleotide RDO system. RDOs for targeted gene correction were first designed in 1996 and are typically 68 nucleotides in length including continuous RNA and DNA sequences RNA is 2 -O-methyl-modified . They have a 25 bp double stranded region homologous to the targeted gene two hairpin ends of T loop and a 5 bp GC clamp that give the molecule much greater stability Fig. 1 . One mismatch site in the middle of the double-stranded region is designed for targeted gene therapy. RDOs have been used recently for targeted gene correction of point mutations both in vitro and in vivo but many problems must be solved before clinical application. One of the solutions is to optimize the delivery vectors for RDOs. To date few RDO delivery systems have been used. Therefore new vectors should be tried for RDO transfer such as the use of nanoparticles. Additionally different kinds of modifications should be applied to RDO carrier systems to increase the total correction efficiency in vivo. Only with the development of delivery systems can RDOs be used for gene therapy and successfully applied to functional genomics. Keywords chimeric RNA-DNA oligonucleotides gene delivery gene therapy targeted gene correction nanoparticles. Targeted gene therapies are ideal strategies for gene therapy which include gene replacement in situ and gene correction. Gene replacement substitutes the mutated gene with a normal one but it is a .

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