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

Kharma, Nawwaf; Varin, Luc; Abu-Baker, Aida; Ouellet, Jonathan; Najeh, Sabrine; Ehdaeivand, Mohammad-Reza; Belmonte, Gabriel; Ambri, Anas; Rouleau, Guy; Perreault, Jonathan (2016). Automated design of hammerhead ribozymes and validation by targeting the PABPN1 gene transcript Nucleic Acids Research , vol. 44 , nº 4. p. 1-12. DOI: 10.1093/nar/gkv1111.

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Résumé

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.

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Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 24 août 2016 15:54
Dernière modification: 24 août 2016 15:54
URI: http://espace.inrs.ca/id/eprint/4521

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