反义寡核酸和人类疾病治疗.pptVIP

Silencing human genetic diseases with oligonucleotide-based therapies Reporter: lanping zheng 2013.10.05 Abstract This review addresses the currently ongoing programs with the aim of developing RNAi and other antisense compounds for the treatment of genetic conditions and the pros and cons that these products may encounter along the The authors have focused on those programs that have reached clinical trials or are very close to do so Nucleicacid-basedtherapies Short interfering rnas sirnas Small hapin rnas(shRNAs Ribozymes DNAzymes Antisense oligonucleotides (ASO) ecos Nucleicacid-basedtherapies DNAzymes and ribozymes: DNAenzymes and ribozymes are oligonucleotides with catalytic activity. The former are synthetic dNa molecules whereas the latter are RNA molecules. Both types of enzymes are able to down-regulate gene expression by binding to and cleaving RNa; in addition, some ribozymes can repair RNa by trans-splicing Nucleicacid-basedtherapies Decoys decoys which are short, double-stranded DNA molecule that contain binding elements that competitively inhibit promoter binding and gene expression have been developed. But have significan tissues affecting their potential clinical use Nucleicacid-basedtherapies Atisense oligonucleotideS(Asos) ASOs are single-stranded fragments of dNA or Rna generally 15-25bp in length designed to bind target mRNA via basepair complementarity and inhibitits translation into protein Although the mechanism is not completely understood, the binding of aso to mRNa is thought to involve steric hindrance of ribosomal movement, activation of endogenous rNaseh for targeted destruction of the dNA/RNA heteroduplex, and conse quent mRNa degradation Nucleicacid-basedtherapies SiRNA: siRNA mediate sequence-specific target selection and subsequent mrna cleavage after recruitment into theRISC (RNA-induced silencing complex enzy-matic complex Inherited diseases addressable by nucleicacid-based drugs Liver diseases (1 Familialhypercholesterolem