Gene Therapy for Inherited Skin Disorders
| Autor: | John A. McGrath, Su M. Lwin |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Gene knockdown medicine.medical_specialty Genetic enhancement Mutant Biology medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Molecular genetics medicine Gene silencing Epidermolysis bullosa Allele Gene |
| Zdroj: | eLS. :1-15 |
| Popis: | Inherited skin disorders are caused by pathogenic mutations in over 500 genes. These mutations result in a spectrum of cutaneous and systemic abnormalities that generate considerable morbidity, and occasionally mortality. To date, however, there are no effective treatments. Nevertheless, the easy accessibility of skin, together with advances in molecular genetics and biotechnology, has paved the way for gene therapy development and testing. Gene therapy aims to reverse the pathology and phenotype of a particular disease through supplementation of the defective gene with a single normal full-length copy or correction of the underlying mutant gene via genome editing or RNA (ribonucleic acid)-based methods. Key Concepts Inherited skin disorders (also known as genodermatoses) encompass a group of genetic skin diseases in which single- or multiple-gene defects account for a wide spectrum of clinical phenotypes with significant physical and psychosocial impact. Epidermolysis bullosa (EB) is a diverse group of autosomal dominant and recessive blistering skin diseases that affects ∼500 000 people worldwide. In EB, relatively minor trauma to the skin causes blistering which can be complicated by delayed healing and scarring. There is a desperate clinical need for effective therapies, including gene therapy. Gene therapy involves manipulation of cellular DNA or RNA to provide therapeutic benefit using various strategies. These include gene modification through gene addition or replacement, and gene correction through RNA-based technologies or genome editing tools. Single-gene disorders are therefore good candidates for gene therapy. The choice of gene therapy strategy in genodermatoses depends on the mode of inheritance and the nature of the pathogenic mutations of a particular disorder. Given that most autosomal recessive skin disorders result in loss of function, deficiency or absence of the wild-type protein, restoring protein function through the addition of a wild-type copy of the mutant gene, or correction of the mutant gene, is an appropriate therapeutic goal. In contrast, heterozygous mutations in dominant skin disorders typically result in dominant-negative interference of the mutant/wild-type proteins. Thus, therapeutic benefits are best sought by knockdown/silencing of the mutant allele while preserving the functional wild-type allele, through applying gene correction techniques using small interfering RNA (siRNA) or gene editing endonucleases. Keywords: skin; genodermatoses; epidermolysis bullosa; gene therapy; gene addition; gene correction; gene editing; vector; lentivirus; retrovirus |
| Databáze: | OpenAIRE |
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