Precision RNAi using synthetic shRNAmir target sites

Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient...

Full description

Saved in:
Bibliographic Details
Main Authors: Thomas Hoffmann, Alexandra Hörmann, Maja Corcokovic, Jakub Zmajkovic, Matthias Hinterndorfer, Jasko Salkanovic, Fiona Spreitzer, Anna Köferle, Katrin Gitschtaler, Alexandra Popa, Sarah Oberndorfer, Florian Andersch, Markus Schaefer, Michaela Fellner, Nicole Budano, Jan G Ruppert, Paolo Chetta, Melanie Wurm, Johannes Zuber, Ralph A Neumüller
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/84792
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849326139394228224
author Thomas Hoffmann
Alexandra Hörmann
Maja Corcokovic
Jakub Zmajkovic
Matthias Hinterndorfer
Jasko Salkanovic
Fiona Spreitzer
Anna Köferle
Katrin Gitschtaler
Alexandra Popa
Sarah Oberndorfer
Florian Andersch
Markus Schaefer
Michaela Fellner
Nicole Budano
Jan G Ruppert
Paolo Chetta
Melanie Wurm
Johannes Zuber
Ralph A Neumüller
author_facet Thomas Hoffmann
Alexandra Hörmann
Maja Corcokovic
Jakub Zmajkovic
Matthias Hinterndorfer
Jasko Salkanovic
Fiona Spreitzer
Anna Köferle
Katrin Gitschtaler
Alexandra Popa
Sarah Oberndorfer
Florian Andersch
Markus Schaefer
Michaela Fellner
Nicole Budano
Jan G Ruppert
Paolo Chetta
Melanie Wurm
Johannes Zuber
Ralph A Neumüller
author_sort Thomas Hoffmann
collection DOAJ
description Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
format Article
id doaj-art-5be3978b927a49d695b800fdcd6cb2bb
institution Kabale University
issn 2050-084X
language English
publishDate 2023-08-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj-art-5be3978b927a49d695b800fdcd6cb2bb2025-08-20T03:48:14ZengeLife Sciences Publications LtdeLife2050-084X2023-08-011210.7554/eLife.84792Precision RNAi using synthetic shRNAmir target sitesThomas Hoffmann0https://orcid.org/0000-0002-1589-0013Alexandra Hörmann1Maja Corcokovic2Jakub Zmajkovic3https://orcid.org/0000-0001-7061-6538Matthias Hinterndorfer4https://orcid.org/0000-0003-2435-4690Jasko Salkanovic5Fiona Spreitzer6Anna Köferle7https://orcid.org/0000-0003-1601-7774Katrin Gitschtaler8Alexandra Popa9Sarah Oberndorfer10Florian Andersch11Markus Schaefer12Michaela Fellner13Nicole Budano14Jan G Ruppert15Paolo Chetta16Melanie Wurm17Johannes Zuber18https://orcid.org/0000-0001-8810-6835Ralph A Neumüller19https://orcid.org/0000-0002-1514-6278Research Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University at Vienna and Medical University of Vienna, Vienna BioCenter (VBC), Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, Vienna, Austria; Medical University of Vienna, Vienna BioCenter, Vienna, AustriaBoehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse, Vienna, AustriaLoss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.https://elifesciences.org/articles/84792cancerRNAiKRASEGFRtarget validationloss-of-function
spellingShingle Thomas Hoffmann
Alexandra Hörmann
Maja Corcokovic
Jakub Zmajkovic
Matthias Hinterndorfer
Jasko Salkanovic
Fiona Spreitzer
Anna Köferle
Katrin Gitschtaler
Alexandra Popa
Sarah Oberndorfer
Florian Andersch
Markus Schaefer
Michaela Fellner
Nicole Budano
Jan G Ruppert
Paolo Chetta
Melanie Wurm
Johannes Zuber
Ralph A Neumüller
Precision RNAi using synthetic shRNAmir target sites
eLife
cancer
RNAi
KRAS
EGFR
target validation
loss-of-function
title Precision RNAi using synthetic shRNAmir target sites
title_full Precision RNAi using synthetic shRNAmir target sites
title_fullStr Precision RNAi using synthetic shRNAmir target sites
title_full_unstemmed Precision RNAi using synthetic shRNAmir target sites
title_short Precision RNAi using synthetic shRNAmir target sites
title_sort precision rnai using synthetic shrnamir target sites
topic cancer
RNAi
KRAS
EGFR
target validation
loss-of-function
url https://elifesciences.org/articles/84792
work_keys_str_mv AT thomashoffmann precisionrnaiusingsyntheticshrnamirtargetsites
AT alexandrahormann precisionrnaiusingsyntheticshrnamirtargetsites
AT majacorcokovic precisionrnaiusingsyntheticshrnamirtargetsites
AT jakubzmajkovic precisionrnaiusingsyntheticshrnamirtargetsites
AT matthiashinterndorfer precisionrnaiusingsyntheticshrnamirtargetsites
AT jaskosalkanovic precisionrnaiusingsyntheticshrnamirtargetsites
AT fionaspreitzer precisionrnaiusingsyntheticshrnamirtargetsites
AT annakoferle precisionrnaiusingsyntheticshrnamirtargetsites
AT katringitschtaler precisionrnaiusingsyntheticshrnamirtargetsites
AT alexandrapopa precisionrnaiusingsyntheticshrnamirtargetsites
AT sarahoberndorfer precisionrnaiusingsyntheticshrnamirtargetsites
AT florianandersch precisionrnaiusingsyntheticshrnamirtargetsites
AT markusschaefer precisionrnaiusingsyntheticshrnamirtargetsites
AT michaelafellner precisionrnaiusingsyntheticshrnamirtargetsites
AT nicolebudano precisionrnaiusingsyntheticshrnamirtargetsites
AT jangruppert precisionrnaiusingsyntheticshrnamirtargetsites
AT paolochetta precisionrnaiusingsyntheticshrnamirtargetsites
AT melaniewurm precisionrnaiusingsyntheticshrnamirtargetsites
AT johanneszuber precisionrnaiusingsyntheticshrnamirtargetsites
AT ralphaneumuller precisionrnaiusingsyntheticshrnamirtargetsites