کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1424744 986735 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeted TFO delivery to hepatic stellate cells
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Targeted TFO delivery to hepatic stellate cells
چکیده انگلیسی

Triplex-forming oligonucleotides (TFOs) represent an antigene approach for gene regulation through direct interaction with genomic DNA. While this strategy holds great promise owing to the fact that only two alleles need silencing to impact gene regulation, delivering TFOs to target cells in vivo is still a challenge. Our recent efforts have focused on conjugating TFOs to carrier molecules like cholesterol to enhance their cellular uptake and mannose-6-phosphate-bovine serum albumin (M6P–BSA) to target TFO delivery to hepatic stellate cells (HSCs) for treating liver fibrosis. These approaches however are rendered less effective owing to a lack of targeted delivery, as seen with lipid-conjugates, and the potential immune reactions due to repeated dosing with high molecular weight BSA conjugated TFO. In this review, we discuss our latest efforts to enhance the effectiveness of TFO for treating liver fibrosis. We have shown that conjugation of TFOs to M6P–HPMA can enhance TFO delivery to HSCs and has the potential to treat liver fibrosis by inhibiting collagen synthesis. This TFO conjugate shows negligible immunogenicity owing to the use of HPMA, one of the least immunogenic copolymers, thereby making it a suitable and more effective candidate for antifibrotic therapy.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 155, Issue 2, 30 October 2011, Pages 326–330
نویسندگان
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