Gene therapy for autosomal dominant disorders of keratin

J Investig Dermatol Symp Proc. 2005 Oct;10(1):47-61. doi: 10.1111/j.1087-0024.2005.10207.x.

Abstract

Dominant mutations that interfere with the assembly of keratin filaments cause painful and disfiguring epidermal diseases like pachyonychia congenita and epidermolysis bullosa simplex. Genetic therapies for such diseases must either suppress the production of the toxic proteins or correct the genetic defect in the chromosome. Because epidermal skin cells may be genetically modified in tissue culture or in situ, gene correction is a legitimate goal for keratin diseases. In addition, recent innovations, such as RNA interference in animals, make an RNA knockdown approach plausible in the near future. Although agents of RNA reduction (small interfering RNA, ribozymes, triplex oligonucleotides, or antisense DNA) can be delivered as nucleotides, the impermeability of the skin to large charged molecules presents a serious impediment. Using viral vectors to deliver genes for selective inhibitors of gene expression presents an attractive alternative for long-term treatment of genetic disease in the skin.

Publication types

  • Review

MeSH terms

  • Animals
  • Darier Disease / genetics
  • Darier Disease / therapy
  • Dependovirus / genetics
  • Ectodermal Dysplasia / genetics
  • Ectodermal Dysplasia / therapy*
  • Epidermolysis Bullosa Simplex / genetics
  • Epidermolysis Bullosa Simplex / therapy
  • Gene Silencing
  • Gene Targeting
  • Genes, Dominant
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Keratins / genetics*
  • Keratoderma, Palmoplantar / genetics
  • Keratoderma, Palmoplantar / therapy*
  • Mice
  • Mutation
  • Nails, Malformed / genetics
  • Nails, Malformed / therapy*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use
  • RNA Interference
  • RNA, Catalytic / genetics
  • RNA, Catalytic / therapeutic use
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use

Substances

  • Oligonucleotides, Antisense
  • RNA, Catalytic
  • RNA, Small Interfering
  • Keratins