Acid-Degradable Cationic Poly(ketal amidoamine) for Enhanced RNA Interference In Vitro and In Vivo

2013 ◽  
Vol 14 (1) ◽  
pp. 240-247 ◽  
Author(s):  
Hyungsuk Lim ◽  
Joungyoun Noh ◽  
Yerang Kim ◽  
Hyungmin Kim ◽  
Jihye Kim ◽  
...  
Keyword(s):  
Rna Interference

scholarly journals Suppression of parathyroid hormone production in vitro and in vivo by RNA interference

2009 ◽  
Vol 75 (5) ◽  
pp. 490-498 ◽  
Author(s):  
Genta Kanai ◽  
Takatoshi Kakuta ◽  
Kaichiro Sawada ◽  
Tun A. Yokoyama ◽  
Reika Tanaka ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Rna Interference ◽  
Hormone Production

scholarly journals In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 758-758
Author(s):  
◽  
Fatima Al-Shahrour ◽  
Kimberly A. Hartwell ◽  
Lisa P Chu ◽  
Jaras Marcus ◽  
...  
Keyword(s):  
Rna Interference ◽  
Cell Growth ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Growth And Survival ◽  
Integrin Beta 3 ◽  
Shrna Screen ◽  
Primary Leukemia

Abstract Abstract 758 Primary leukemia stem cells (LSCs) reside in an in vivo microenvironment that supports the growth and survival of malignant cells. Despite the increasing understanding of the importance of niche interactions and primary cell biology in leukemia, many studies continue to focus on cell autonomous processes in artificial model systems. The majority of strategies to-date that attempt to define therapeutic targets in leukemia have relied on screening cell lines in culture; new strategies should incorporate the use of primary disease within a physiologic niche. Using a primary murine MLL-AF9 acute myeloid leukemia (AML) model highly enriched for LSCs, we performed an in vivo short hairpin RNA (shRNA) screen to identify novel genes that are essential for leukemia growth and survival. LSCs infected with pools of shRNA lentivirus were transplanted and grown in recipient mice for 2 weeks, after which bone marrow and spleen cells were isolated. Massively parallel sequencing of infected LSCs isolated before and after transplant was used to quantify the changes in shRNA representation over time. Our in vivo screens were highly sensitive, robust, and reproducible and identified a number of positive controls including genes required for MLL-AF9 transformation (Ctnnb1, Mef2c, Ccna1), genes universally required for cell survival (Ube2j2, Utp18), and genes required in other AML models (Myb, Pbx1, Hmgb3). In our primary and validation screens, multiple shRNAs targeting Integrin Beta 3 (Itgb3) were consistently depleted by more than 20-fold over two weeks in vivo. Follow up studies using RNA interference (RNAi) and Itgb3−/− mice identified Itgb3 as essential for murine leukemia cells growth and transformation in vivo, and loss of Itgb3 conferred a statistically significant survival advantage to recipient mice. Importantly, neither Itgb3 knockdown or genetic loss impaired normal hematopoietic stem and progenitor cell (HSPC) function in 16 week multilineage reconstitution assays. We further identified Itgav as the heterodimeric partner of Itgb3 in our model, and found that knockdown of Itgav inhibited leukemia cell growth in vivo. Consistent the therapeutic aims or our study, flow cytometry on primary human AML samples revealed ITGAV/ITGB3 heterodimer expression. To functionally assess the importance of gene expression in a human system, we performed another RNAi screen on M9 leukemia cells, primary human cord blood CD34+ cells transduced with MLL-ENL that are capable of growing in vitro or in a xenotransplant model in vivo. We found that ITGB3 loss inhibited M9 cell growth in vivo, but not in vitro, consistent with the importance of ITGB3 in a physiologic microenvironment. We explored the signaling pathways downstream of Itgb3 using an additional in vivo, unbiased shRNA screen and identified Syk as a critical mediator of Itgb3 activity in leukemia. Syk knockdown by RNAi inhibited leukemia cell growth in vivo; downregulation of Itgb3 expression resulted in decreased levels of Syk phosphorylation; and expression of an activated form of Syk, TEL-SYK, rescued the effects of Itgb3 knockdown on leukemia cell growth in vivo. To understand cellular processes controlled by Itgb3, we performed gene expression studies and found that, in leukemia cells, Itgb3 knockdown induced differentiation and inhibited multiple previously published LSC transcriptional programs. We confirmed these results using primary leukemia cell histology and a model system of leukemia differentiation. Finally, addition of a small molecule Syk inhibitor, R406, to primary cells co-cultured with bone marrow stroma caused a dose-dependent decrease in leukemia cell growth. Our results establish the significance of the Itgb3 signaling pathway, including Syk, as a potential therapeutic target in AML, and demonstrate the utility of in vivo RNA interference screens. Disclosures: Armstrong: Epizyme: Consultancy.

Inhibition of HPV 16 E6 oncogene expression by RNA interference in vitro and in vivo

2006 ◽  
Vol 16 (2) ◽  
pp. 743-751 ◽  
Author(s):  
X.-Y. NIU ◽  
Z.-L. PENG ◽  
W.-Q. DUAN ◽  
H. WANG ◽  
P. WANG
Keyword(s):  
Rna Interference ◽  
Hpv 16 ◽  
Oncogene Expression

RNA interference of osteopontin inhibits in vitro and in vivo colon cancer metastasis

2004 ◽  
Vol 121 (2) ◽  
pp. 300
Author(s):  
P.Y. Wai ◽  
Z. Mi ◽  
H. Guo ◽  
S. Sarraf-Yazdi ◽  
B. Clary ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Rna Interference ◽  
Cancer Metastasis ◽  
Colon Cancer Metastasis

scholarly journals miR-150-Based RNA Interference Attenuates Tubulointerstitial Fibrosis through the SOCS1/JAK/STAT Pathway In Vivo and In Vitro

2020 ◽  
Vol 22 ◽  
pp. 871-884
Author(s):  
Junjun Luan ◽  
Jingqi Fu ◽  
Dongdong Wang ◽  
Congcong Jiao ◽  
Xiangfei Cui ◽  
...  
Keyword(s):  
Rna Interference ◽  
Tubulointerstitial Fibrosis ◽  
Stat Pathway

scholarly journals Lentivirus‑mediated RNA interference targeting EBNA1 gene inhibits the growth of GT‑38 cells in�vitro and in�vivo

2019 ◽  
Author(s):  
Jian Wang ◽  
Cunfu Liang ◽  
Fansheng Meng ◽  
Xiangwen Xu ◽  
Yan Wu ◽  
...  
Keyword(s):  
Rna Interference ◽  
Ebna1 Gene

scholarly journals RNA interference-mediated gene silencing in murine T cells: in vitro and in vivo validation of proinflammatory target genes

2008 ◽  
Vol 6 (1) ◽  
pp. 3 ◽  
Author(s):  
Tatjana C Gust ◽  
Luisa Neubrandt ◽  
Claudia Merz ◽  
Khusru Asadullah ◽  
Ulrich Zügel ◽  
...  
Keyword(s):  
T Cells ◽  
Rna Interference ◽  
Gene Silencing ◽  
Target Genes ◽  
In Vivo Validation

scholarly journals Downregulation of CD147 expression by RNA interference inhibits HT29 cell proliferation, invasion and tumorigenicity in vitro and in vivo

2013 ◽  
Vol 43 (6) ◽  
pp. 1885-1894 ◽  
Author(s):  
RUI LI ◽  
YUQIN PAN ◽  
BANGSHUN HE ◽  
YEQIONG XU ◽  
TIANYI GAO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Rna Interference ◽  
Ht29 Cell ◽  
Cd147 Expression
Sign in / Sign up

Export Citation Format

Share Document