کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1934921 | 1050653 | 2008 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing](/preview/png/1934921.png)
چکیده انگلیسی
The high genetic diversity and mutability of HIV pose a major problem for RNAi-mediated antiviral therapy. Simultaneous targeting of multiple highly conserved viral sequences has been suggested for durable cross-clade inhibition. Here we validate the approach of co-targeting two conserved sequences in the Tat and Vif genes. When coexpressed as artificial microRNA from a PolII driven miR-155-based vector, the sequences together mediated effective and sustained inhibition of HIV replication without virus breakout. To understand the nature of this efficient control, we analyzed genome sequences of 625 HIV-1 isolates in the Los Alamos Sequence database. Interestingly most natural variants were capable of wobble binding with the Tat/Vif siRNAs. Efficient silencing of reporter luciferase constructs bearing these variants residues verified that the Tat/Vif sequences together tolerated wobble binding and mediated functional RNAi. We propose the rationale of targeting highly conserved HIV sequences where wobble substitutions permit functional RNAi for global HIV repression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 374, Issue 2, 19 September 2008, Pages 214-218
Journal: Biochemical and Biophysical Research Communications - Volume 374, Issue 2, 19 September 2008, Pages 214-218
نویسندگان
Jiyeon Son, Pradeep D. Uchil, Young Bong Kim, Premlata Shankar, Priti Kumar, Sang-Kyung Lee,