Gene therapy for retinal disease



  • Gene therapy can be considered a method of drug delivery. Gene therapy takes advantage of the host organism’s gene transcription/translation machinery to locally produce bioactive substances. In gene therapy, a nucleic acid compound (DNA or RNA) is delivered to the target tissue via a vector system. The nucleic acid can directly affect gene expression by binding to homologous nucleic acid sequences within the cell. Such a phenomenon is used in “antisense” strategies. Alternatively, the target cells will transcribe the delivered DNA transgene (or the reversetranscribed RNA template) to produce RNA, which may be bioactive itself, or may be translated to a protein with bioactive properties. The greatest technical challenge is to achieve efficient and stable expression of the introduced cDNA. This is largely a function of the vector system used to introduce the exogenous nucleic acid sequence (Table 1). In some instances, injection of naked DNA oligonucleotides alone into host tissue will result in a biological effect. Robinson et al. injected DNA oligonucleotides that were antisense to a target vascular endothelial growth factor (VEGF) molecule and obtained evidence for therapeutic effect in a mouse model of retinopathy of prematurity (1). Cellular uptake and stability of such molecules is inefficient, however. Therefore, a variety of physiochemical and biological means have been developed with which to enhance the efficiency of nucleic acid delivery into various target cells. Examples include encapsulation in liposomes, addition of lipid/cationic compounds to the nucleic acids, electroporation, use of immunoliposomes, high-pressure injection, and bombardment of tissue with gold particles coated with DNA using a “gene gun” (Table 1). The most commonly employed vector system in gene therapy, however, is that of genetically modified viruses (Table 1). Viruses are highly efficient at transfer of exogenous DNA into host tissue.
  • Authors

    International Standard Book Number (isbn) 13

  • 9780824728601
  • Start Page

  • 157
  • End Page

  • 174