| Local Delivery of Gene-Modifying Triplex-Forming Molecules to the Epidermis. | |
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MedLine Citation:
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PMID: 23014335 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Epidermal keratinocytes are particularly suitable candidates for in situ gene correction. Intraperitoneal administration of a triplex-forming oligonucleotide (TFO) was previously shown to introduce DNA base changes in a reporter gene in skin, without identifying which cells had been targeted. We extend those previous experiments using two triplex-forming molecules, a peptide nucleic acid-antennapedia (PNA-Antp), and a TFO (AG30), as well as two lines of transgenic mice that have the chromosomally integrated λsupFG1 shuttle-reporter transgene. Successful in vivo genomic modification occurs in the epidermis and dermis in CD1 transgenic mice following either intraperitoneal or intradermal delivery of the PNA-Antp conjugate. FITC-PNA-Antp accumulates in nuclei of keratinocytes, and, after intradermal delivery of the PNA-Antp, chromosomally modified, keratin 5-positive basal keratinocytes persist for at least 10 days. In hairless (SKH1) mice with the λsupFG1 transgene, intradermal delivery of the TFO, AG30, introduces gene modifications in both tail and back skin, and these chromosomal modifications persist in basal keratinocytes for 10 days. Hairless mice should facilitate comparison of various targeting agents and methods of delivery. Gene targeting by repeated local administration of oligonucleotides may prove clinically useful for judiciously selected disease-causing genes in the epidermis.Journal of Investigative Dermatology advance online publication, 27 September 2012; doi:10.1038/jid.2012.351. |
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Authors:
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Faye A Rogers; Rong-Hua Hu; Leonard M Milstone |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-27 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: - ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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