Literature DB >> 23792574

"Selective cell death mediated by small conditional RNAs" is not selective.

Kalpesh Patel1, Scott E Kern.   

Abstract

Small conditional RNAs were used to kill cells selectively in a prior report. The method utilized the cellular innate immune response to dsRNA, causing PKR activation and cell death. We designed small conditional RNAs specific to a highly restricted transcript, that of the mesothelin gene expressed in various cancer lines and specific to a tpc/hpr fusion transcript expressed in a published "control" line. Hairpins of small conditional RNAs were functionally active in cell-free conditions. Hairpins were transfected into 6 types of cells. We observed non-specific killing of cells after transfection of the hairpins targeting the reported fusion transcript or of the mesothelin transcript. Thus when attempting to use this system for a special purpose, to target cancer mutations, the results were not satisfactory. Specifically when repeating the work described in the publication, we could not replicate the results using the methods described. Recently the publication was retracted but without comment on the validity of the reported method. Here we provide scientific basis to consider the method impaired or invalid.

Entities:  

Keywords:  PKR; RNA hairpin; cell death; dsRNA; hybridization chain reaction; innate immune response; small conditional RNAs

Mesh:

Substances:

Year:  2013        PMID: 23792574      PMCID: PMC3841206          DOI: 10.4161/cbt.25093

Source DB:  PubMed          Journal:  Cancer Biol Ther        ISSN: 1538-4047            Impact factor:   4.742


  9 in total

1.  Triggered amplification by hybridization chain reaction.

Authors:  Robert M Dirks; Niles A Pierce
Journal:  Proc Natl Acad Sci U S A       Date:  2004-10-18       Impact factor: 11.205

2.  Structural analysis of the cancer-specific promoter in mesothelin and in other genes overexpressed in cancers.

Authors:  Yunzhao R Ren; Kalpesh Patel; Bogdan C Paun; Scott E Kern
Journal:  J Biol Chem       Date:  2011-02-02       Impact factor: 5.157

3.  Selective leukemia cell death by activation of the double-stranded RNA-dependent protein kinase PKR.

Authors:  Ya-Juan Li; Jian-Ming Zeng; Shi-Feng Huang; Xiao-Zhong Wang; Shi-Qiao Zhao; Wei-Jun Bai; Wei-Xi Cao; Zong-Gan Huang; Wen-Li Feng
Journal:  Int J Mol Med       Date:  2011-04-04       Impact factor: 4.101

4.  Selective cell death mediated by small conditional RNAs.

Authors:  Suvir Venkataraman; Robert M Dirks; Christine T Ueda; Niles A Pierce
Journal:  Proc Natl Acad Sci U S A       Date:  2010-09-07       Impact factor: 11.205

5.  Inhibition of glioma growth by tumor-specific activation of double-stranded RNA-dependent protein kinase PKR.

Authors:  Alexei Shir; Alexander Levitzki
Journal:  Nat Biotechnol       Date:  2002-08-19       Impact factor: 54.908

Review 6.  The dsRNA protein kinase PKR: virus and cell control.

Authors:  M A García; E F Meurs; M Esteban
Journal:  Biochimie       Date:  2007-03-12       Impact factor: 4.079

7.  Sodium boric acid: a Tris-free, cooler conductive medium for DNA electrophoresis.

Authors:  Jonathan R Brody; Scott E Kern
Journal:  Biotechniques       Date:  2004-02       Impact factor: 1.993

8.  Programmable in situ amplification for multiplexed imaging of mRNA expression.

Authors:  Harry M T Choi; Joann Y Chang; Le A Trinh; Jennifer E Padilla; Scott E Fraser; Niles A Pierce
Journal:  Nat Biotechnol       Date:  2010-10-31       Impact factor: 54.908

9.  EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice.

Authors:  Alexei Shir; Manfred Ogris; Ernst Wagner; Alexander Levitzki
Journal:  PLoS Med       Date:  2005-12-06       Impact factor: 11.069

  9 in total

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