Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA

Adv Drug Deliv Rev. 2006 Nov 15;58(11):1203-23. doi: 10.1016/j.addr.2006.07.020. Epub 2006 Sep 15.

Abstract

Nucleic acids have gained a lot of interest for the treatment of ocular diseases. The first to enter in clinic has been Vitravene an antisense oligonucleotide for the treatment of cytomegalovirus (CMV) infection and more recently, research on aptamers have led to the marketing of anti-vascular endothelial growth factor (VEGF) inhibitor (Macugen) for the treatment of age-related macular degeneration (AMD). The siRNAs appear very promising as they are very potent inhibitors of protein expression. Despite their potential, nucleic acids therapeutic targets of nucleic acid-based drugs are mainly located in the posterior segment of the eye requiring invasive administration which can be harmful if repeated. Their intracellular penetration in some cases needs to be enhanced. This is the reason why adequate delivery systems were designed either to insure cellular penetration, protection against degradation or to allow long-term delivery. A combination of both effects was also developed for an implantable system. In conclusion, the intraocular administration of nucleic acids offers interesting perspectives for the treatment of ocular diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Aptamers, Nucleotide / administration & dosage*
  • Aptamers, Nucleotide / metabolism
  • Drug Delivery Systems*
  • Eye Diseases / drug therapy*
  • Eye Diseases / metabolism
  • Humans
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / metabolism
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / metabolism

Substances

  • Aptamers, Nucleotide
  • Oligonucleotides, Antisense
  • RNA, Small Interfering