Engineering siRNA therapeutics: challenges and strategies

Small interfering RNA (siRNA) is a potential method of gene silencing to target specific genes. Although the U.S. Food and Drug Administration (FDA) has approved multiple siRNA-based therapeutics, many biological barriers limit their use for treating diseases. Such limitations include challenges concerning systemic or local administration, short half-life, rapid clearance rates, nonspecific binding, cell membrane penetration inability, ineffective endosomal escape, pH sensitivity, endonuclease degradation, immunological responses, and intracellular trafficking. To overcome these barriers, various strategies have been developed to stabilize siRNA, ensuring their delivery to the target site. Chemical…

• NN
  National Natural Science Foundation of China

  Awards: 51903202, 82370903, 22205201, 51903202, 82370903, 22205201
• NS
  Natural Science Foundation of Shaanxi Province

  Award: 2020JM-055
• FR
  Fundamental Research Funds for the Central Universities

  Award: xtr042019020
• NS
  Natural Science Foundation of Zhejiang Province

  Award: LZ23H180003