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锤头状核酶的自动化设计及通过靶向PABPN1基因转录本进行验证。

Automated design of hammerhead ribozymes and validation by targeting the PABPN1 gene transcript.

作者信息

Kharma Nawwaf, Varin Luc, Abu-Baker Aida, Ouellet Jonathan, Najeh Sabrine, Ehdaeivand Mohammad-Reza, Belmonte Gabriel, Ambri Anas, Rouleau Guy, Perreault Jonathan

机构信息

Electrical & Computer Eng. Dept., Concordia University, 1455 boul. de Maisonneuve O., Montreal, QC, H3G 1M8, Canada

Biology Department, Concordia University, 7141 rue Sherbrooke O., Montreal, QC, H4B 1R6, Canada.

出版信息

Nucleic Acids Res. 2016 Feb 29;44(4):e39. doi: 10.1093/nar/gkv1111. Epub 2015 Nov 2.

DOI:10.1093/nar/gkv1111
PMID:26527730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4770207/
Abstract

We present a new publicly accessible web-service, RiboSoft, which implements a comprehensive hammerhead ribozyme design procedure. It accepts as input a target sequence (and some design parameters) then generates a set of ranked hammerhead ribozymes, which target the input sequence. This paper describes the implemented procedure, which takes into consideration multiple objectives leading to a multi-objective ranking of the computer-generated ribozymes. Many ribozymes were assayed and validated, including four ribozymes targeting the transcript of a disease-causing gene (a mutant version of PABPN1). These four ribozymes were successfully tested in vitro and in vivo, for their ability to cleave the targeted transcript. The wet-lab positive results of the test are presented here demonstrating the real-world potential of both hammerhead ribozymes and RiboSoft. RiboSoft is freely available at the website http://ribosoft.fungalgenomics.ca/ribosoft/.

摘要

我们展示了一种新的可公开访问的网络服务RiboSoft，它实现了一个全面的锤头状核酶设计程序。它接受一个目标序列（以及一些设计参数）作为输入，然后生成一组针对输入序列的排名锤头状核酶。本文描述了所实施的程序，该程序考虑了多个目标，从而对计算机生成的核酶进行多目标排名。对许多核酶进行了测定和验证，包括四种针对致病基因（PABPN1的突变版本）转录本的核酶。这四种核酶在体外和体内均成功测试了其切割目标转录本的能力。此处展示了测试的湿实验室阳性结果，证明了锤头状核酶和RiboSoft在现实世界中的潜力。可在网站http://ribosoft.fungalgenomics.ca/ribosoft/免费获取RiboSoft。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/39ad196a175f/gkv1111fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/b0b8dbdd5b5c/gkv1111fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/f11ba2e91efd/gkv1111fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/5d703d2bb545/gkv1111fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/68eb32eb09e4/gkv1111fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/17b80744003f/gkv1111fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/eef815885ea7/gkv1111fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/39ad196a175f/gkv1111fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/b0b8dbdd5b5c/gkv1111fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/f11ba2e91efd/gkv1111fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/5d703d2bb545/gkv1111fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/68eb32eb09e4/gkv1111fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/17b80744003f/gkv1111fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/eef815885ea7/gkv1111fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c1/4770207/39ad196a175f/gkv1111fig8.jpg

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