کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6078358 | 1203567 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Use of Self-Delivery siRNAs to Inhibit Gene Expression in an Organotypic Pachyonychia Congenita Model
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موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
Although RNA interference offers therapeutic potential for treating skin disorders, delivery hurdles have hampered clinical translation. We have recently demonstrated that high pressure, resulting from intradermal injection of large liquid volumes, facilitated nucleic acid uptake by keratinocytes in mouse skin. Furthermore, similar intradermal injections of small interfering RNA (siRNA; TD101) into pachyonychia congenita (PC) patient foot lesions resulted in improvement. Unfortunately, the intense pain associated with hypodermic needle administration to PC lesions precludes this as a viable delivery option for this disorder. To investigate siRNA uptake by keratinocytes, an organotypic epidermal model, in which pre-existing endogenous gene or reporter gene expression can be readily monitored, was used to evaluate the effectiveness of “self-delivery” siRNA (i.e., siRNA chemically modified to enhance cellular uptake). In this model system, self-delivery siRNA treatment resulted in reduction of pre-existing fluorescent reporter gene expression under conditions in which unmodified controls had little or no effect. Additionally, treatment of PC epidermal equivalents with self-delivery “TD101” siRNA resulted in marked reduction of mutant keratin 6a mRNA with little or no effect on wild-type expression. These results indicate that chemical modification of siRNA may overcome certain limitations to transdermal delivery (specifically keratinocyte uptake) and may have clinical utility for inhibition of gene expression in the skin.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 131, Issue 5, May 2011, Pages 1037-1044
Journal: Journal of Investigative Dermatology - Volume 131, Issue 5, May 2011, Pages 1037-1044
نویسندگان
Robyn P. Hickerson, Manuel A. Flores, Devin Leake, Maria F. Lara, Christopher H. Contag, Sancy A. Leachman, Roger L. Kaspar,