کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550523 1557294 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The absorption enhancer sodium deoxycholate promotes high gene transfer in skeletal muscles
ترجمه فارسی عنوان
افزایش دهنده جذب سدیم دگزیکسولات باعث انتقال ژن بالا در عضلات اسکلتی می شود
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

Gene delivery to skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. In addition, muscle is an attractive target tissue because it is easily accessible. However, very few synthetic vectors proved capable of surpassing naked DNA mediated muscle gene transfer. In fact, only neutral copolymers, in particular poloxamers, demonstrated capacities to increase transgene expression in skeletal muscles. Here, we studied in vitro and in vivo behaviour of different bile salts. We report that sodium deoxycholate (DOC) and derivatives thereof increase after intramuscular injection by more than 100-fold the levels of the reporter gene luciferase compared to naked DNA. Using a LacZ expression cassette, we found that more than 20% of the muscle fibers expressed the reporter gene. Prolonged expression of a secreted reporter gene derived from a natural murine alkaline phosphatase enzyme could be documented. Altogether, our results demonstrate that bile salts belong to the most efficient chemicals identified so far for skeletal muscle gene transfer. Importantly, since these compounds are naturally found in the body, there is no risk of immune response against them and in addition several bile salts are already used in human medicine. Bile salt mediated muscle gene transfer may thus have broad applications in gene therapy.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 523, Issue 1, 15 May 2017, Pages 291-299
نویسندگان
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