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| phi C31 integrase-mediated nonviral genetic correction of junctional epidermolysis bullosa |
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| Author(s): Ortiz-Urda S, Thyagarajan B, Keene DR, Lin Q, Calos MP, Khavari PA |
| Source: HUMAN GENE THERAPY Volume: 14 Issue: 9 Pages: 923-928 Published: JUN 2003 |
| Times Cited: 47 References: 27 |
| Abstract: Patients afflicted with severe laminin 5-deficient junctional epidermolysis bullosa ( JEB) often die in infancy with massive cutaneous blistering. Prior approaches to genetically correct this disorder have relied on stable integration of wild-type LAMB3 sequences, using retroviral vectors. To develop a nonviral approach to JEB gene therapy, we used the phi31 integrase, which mediates unidirectional genomic integration of plasmids containing a specific attB site. An attB-containing laminin 5 beta3 expression plasmid was integrated into the genomes of primary keratinocytes from four unrelated, genetically characterized JEB patients. phi31 integrase supported genomic integration into epidermal progenitor cells. Regeneration of human skin on immunedeficient mice, using these cells, produced human skin tissue with restored laminin 5 expression. Furthermore, corrected JEB tissue restored hemidesmosome formation and abolished histologic evidence of subepidermal blistering. These findings provide an approach to durable nonviral correction of JEB. |
| Document Type: Article |
| Language: English |
| Reprint Address: Khavari, PA (reprint author), Stanford Univ, Program Epithelial Biol, Sch Med, 269 Campus Dr,Room 2145, Stanford, CA 94305 USA |
Addresses:
1. Stanford Univ, Program Epithelial Biol, Sch Med, Stanford, CA 94305 USA
2. Stanford Univ, VA Palo Alto Healthcare Syst, Sch Med, Stanford, CA 94305 USA
3. Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA
4. Shriners Hosp Children, Portland, OR 97201 USA |
| Publisher: MARY ANN LIEBERT INC PUBL, 2 MADISON AVENUE, LARCHMONT, NY 10538 USA |
| Subject Category: Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental |
| IDS Number: 690CA |
| ISSN: 1043-0342 |
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