Optimizing the delivery systems of chimeric RNA.DNA oligonucleotides.
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.
Liang
Li
L
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.
Liu
De-Pei
DP
Liang
Chih-Chuan
CC
D002678:Chimera; D004247:DNA / Q000008:administration & dosage*; D015316:Genetic Therapy; D006801:Humans; D012313:RNA / Q000008:administration & dosage*
D012313:RNA; D004247:DNA