Cutaneous gene transfer for skin and systemic diseases

Abstract

This article is partially based on the findings presented at a symposium on Cutaneous Gene Therapy, held in Uppsala, September 2001, and abstracted in Acta Derm Venereol 81: 227–239. Abstract. Khavari PA, Rollman O, Vahlquist A (Stanford University School of Medicine, Stanford, CA, USA; and Department of Medical Sciences, Dermatology, Uppsala University, Uppsala, Sweden). Cutaneous gene transfer for skin and systemic diseases (Review). J Intern Med 2002; 252: 1–10. Recent progress in molecular genetics has illuminated the basis for a wide variety of inherited and acquired diseases. Gene therapy offers an attractive therapeutic approach capitalizing upon these new mechanistic insights. The skin is a uniquely attractive tissue site for development of new genetic therapeutic approaches both for its accessibility as well as for the large number of diseases that are amenable in principle to cutaneous gene transfer. Amongst these opportunities are primary monogenic skin diseases, chronic wounds and systemic disorders characterized by low or absent levels of circulating polypeptides. For cutaneous gene therapy to be effective, however, significant progress is required in a number of domains. Recent advances in vector design, administration, immune modulation, and regulation of gene expression have brought the field much nearer to clinical utility.

Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters

“…wiley.co.uk/genmed/clinical/). Although skin represents a promising target (due to large unmet clinical needs, easy access to tissue and relative ease of monitoring 1 ), only a few clinical trials have been carried out in the last decade, with the majority related to the treatment of melanoma. 2,3 A large number of genetic skin disorders, that have few if any treatment options, are amenable to gene therapy [4][5][6][7] but efforts to translate such approaches to the clinic are hampered by the difficulty of delivering nucleic acids across tissue and cellular barriers.…”

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

“…Also, this research was made possible due to the harvest and cultivation ease of fibroblast and keratinocyte, thus allowing in vitro testing for gene transfer and the use of skin cells as vehicles in gene transfer [192]. Gene delivery has also been explored as an alternative to growth factor delivery because infiltrating cells uptake the genes and produce continuously the therapeutic protein(s) in the local environment [193,194].…”

siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model

“…6,7 Skin represents an ideal target for siRNA therapies due to its accessibility and the large number of monogenic dominant negative skin disorders. [8][9][10] It is estimated that in the general population as many as one person in 3000 suffers from diseases resulting from pathogenic keratin mutations. 11 The first siRNA clinical trial in skin (for treatment of the rare skin disorder pachyonychia congenita) has recently been completed, with encouraging results (unpublished data and Leachman et al 10 ).…”