Journal ArticleDOI
Induction of an interferon response by RNAi vectors in mammalian cells
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TLDR
It is reported here that a substantial number of shRNA vectors can trigger an interferon response and is thought to be too short to induce interferons expression.Abstract:
DNA vectors that express short hairpin RNAs (shRNAs) from RNA polymerase III (Pol III) promoters are a promising new tool to reduce gene expression in mammalian cells. shRNAs are processed to small interfering RNAs (siRNAs) of 21 nucleotides (nt) that guide the cleavage of the cognate mRNA by the RNA-induced silencing complex. Although siRNAs are thought to be too short to induce interferon expression, we report here that a substantial number of shRNA vectors can trigger an interferon response.read more
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Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).
Journal ArticleDOI
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
TL;DR: It is demonstrated that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5, an additional cellular cofactor required for miRNA biogenesis and function.
Journal ArticleDOI
Asymmetry in the assembly of the RNAi enzyme complex.
TL;DR: It is shown that the two strands of an siRNA duplex are not equally eligible for assembly into RISC, and it is suggested that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed.
Journal ArticleDOI
Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
Jürgen Soutschek,Akin Akinc,Birgit Bramlage,Klaus Charisse,Rainer Constien,Mary Donoghue,Sayda Elbashir,Anke Geick,Philipp Hadwiger,Jens Harborth,Matthias John,Venkitasamy Kesavan,Gary Lavine,Rajendra K. Pandey,Timothy Racie,Kallanthottathil G. Rajeev,Ingo Röhl,Ivanka Toudjarska,Gang Wang,Silvio Wuschko,David Bumcrot,Victor Koteliansky,Stefan Limmer,Muthiah Manoharan,Hans-Peter Vornlocher +24 more
TL;DR: In this article, chemically modified short interfering RNAs (siRNAs) were used to silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice.
Journal ArticleDOI
Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA.
TL;DR: It is reported that synthetic siRNAs formulated in nonviral delivery vehicles can be potent inducers of interferons and inflammatory cytokines both in vivo in mice and in vitro in human blood.
References
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Journal ArticleDOI
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Luigi Naldini,Ulrike Blömer,Philippe Gallay,Daniel S. Ory,Richard C. Mulligan,Fred H. Gage,Inder M. Verma,Didier Trono +7 more
TL;DR: The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy.
Journal ArticleDOI
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
TL;DR: It is shown that siRNA expression mediated by this vector causes efficient and specific down-regulation of gene expression, resulting in functional inactivation of the targeted genes.
Journal ArticleDOI
Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.
David F. Stojdl,Brian D. Lichty,Shane Knowles,Ricardo Marius,Harold L. Atkins,Nahum Sonenberg,John C. Bell +6 more
TL;DR: Vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon, is used as a replication-competent oncolytic virus and a new strategy for the treatment of interferons non-responsive tumors is demonstrated.
Journal ArticleDOI
Identification of a Gene That Reverses the Immortal Phenotype of a Subset of Cells and Is a Member of a Novel Family of Transcription Factor-Like Genes
Michael J. Bertram,Nathalie G. Bérubé,X. Hang-Swanson,Qitao Ran,J. K. Leung,S. Bryce,K. Spurgers,Roger J. Bick,Antonio Baldini,Yi Ning,L. J. Clark,E. K. Parkinson,J. C. Barrett,James R. Smith,Olivia M. Pereira-Smith +14 more
TL;DR: The cloning and identification of a gene, mortality factor 4 (MORF 4), is reported, which induces a senescent-like phenotype in immortal cell lines assigned to complementation group B with concomitant changes in two markers for senescence.
Journal ArticleDOI
Role for the Mortality Factors MORF4, MRGX, and MRG15 in Transcriptional Repression via Associations with Pf1, mSin3A, and Transducin-Like Enhancer of Split
Gregory S. Yochum,Donald E. Ayer +1 more
TL;DR: It is shown that mSin3A and TLE interact with members of the mortality factor (MORF) family of putative transcriptional regulators, and that common functions of the MORFs are likely elicited through the action of a MORF/m Sin3A/TLE complex.