Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo

被引：30

作者：

Hsu, David S. ^{[1
,2
,3
]}

Kornepati, Anand V. R. ^{[1
,2
,3
]}

Glover, Wayne ^{[1
,2
,3
]}

Kennedy, Edward M. ^{[1
,2
,3
]}

Cullen, Bryan R. ^{[1
,2
,3
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Duke Canc Inst, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Med Genet, Duke Canc Inst, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Microbiol, Duke Canc Inst, Durham, NC 27710 USA

来源：

FUTURE VIROLOGY | 2018年 / 13卷 / 07期

关键词：

adeno-associated virus vectors; anal tumors; CRISPR/Cas; gene therapy; human papillomavirus; CERVICAL-CARCINOMA CELLS; HUMAN-PAPILLOMAVIRUS E6; COLORECTAL-CANCER; XENOGRAFTS; MODEL; TRIAL;

D O I：

10.2217/fvl-2018-0010

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Aim: The goal of this study was to determine if a single AAV vector, encoding Cas9 and guide RNAs specific for the HPV16 E6 and E7 genes, could inhibit the growth of an HPV16-induced tumor in vivo. Materials & methods: We grew HPV16(+), patient-derived anal cancer explants in immunodeficient mice and then challenged these by injection of AAV-based vectors encoding Cas9 and control or HPV16-specific guide RNAs. Results & conclusion: We observed a significant and selective reduction in tumor growth when the HPV16 E6 and E7 genes were targeted using Cas9. These studies provide proof of principle for the hypothesis that CRISPR/Cas has the potential to be used to selectively treat HPV-induced tumors in humans.

引用

页码：475 / 482

页数：8

共 23 条

[1] Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal - A randomized controlled trial [J].

Ajani, Jaffer A. ;

Winter, Kathryn A. ;

Gunderson, Leonard L. ;

Pedersen, John ;

Benson, Al B., III ;

Thomas, Charles R., Jr. ;

Mayer, Robert J. ;

Haddock, Michael G. ;

Rich, Tyvin A. ;

Willett, Christopher .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 299 (16) :1914-1921

[2] A Molecularly Annotated Platform of Patient-Derived Xenografts ("Xenopatients") Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer [J].

Bertotti, Andrea ;

Migliardi, Giorgia ;

Galimi, Francesco ;

Sassi, Francesco ;

Torti, Davide ;

Isella, Claudio ;

Cora, Davide ;

Di Nicolantonio, Federica ;

Buscarino, Michela ;

Petti, Consalvo ;

Ribero, Dario ;

Russolillo, Nadia ;

Muratore, Andrea ;

Massucco, Paolo ;

Pisacane, Alberto ;

Molinaro, Luca ;

Valtorta, Emanuele ;

Sartore-Bianchi, Andrea ;

Risio, Mauro ;

Capussotti, Lorenzo ;

Gambacorta, Marcello ;

Siena, Salvatore ;

Medico, Enzo ;

Sapino, Anna ;

Marsoni, Silvia ;

Comoglio, Paolo M. ;

Bardelli, Alberto ;

Trusolino, Livio .

CANCER DISCOVERY, 2011, 1 (06) :508-523

[3] Establishment of human colon cancer cell lines from fresh tumors versus xenografts: Comparison of success rate and cell line features [J].

Dangles-Marie, Virginie ;

Pocard, Marc ;

Richon, Sophie ;

Weiswald, Louis-Bastien ;

Assayag, Franck ;

Saulnier, Patrick ;

Judde, Jean-Gabriel ;

Janneau, Jean-Louis ;

Auger, Nathalie ;

Validire, Pierre ;

Dutrillaux, Bernard ;

Praz, Francoise ;

Bellet, Dominique ;

Poupon, Marie-France .

CANCER RESEARCH, 2007, 67 (01) :398-407

[4] Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells [J].

DeFilippis, RA ;

Goodwin, EC ;

Wu, LL ;

DiMaio, D .

JOURNAL OF VIROLOGY, 2003, 77 (02) :1551-1563

[5] Anticancer drug response and expression of molecular marker in early-passage xenotransplanted colon carcinomas [J].

Fichtner, I ;

Slisow, W ;

Gill, J ;

Becker, M ;

Elbe, B ;

Hillebrand, T ;

Bibby, M .

EUROPEAN JOURNAL OF CANCER, 2004, 40 (02) :298-307

[6] Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications [J].

Friedland, Ari E. ;

Baral, Reshica ;

Singhal, Pankhuri ;

Loveluck, Katherine ;

Shen, Shen ;

Sanchez, Minerva ;

Marco, Eugenio ;

Gotta, Gregory M. ;

Maeder, Morgan L. ;

Kennedy, Edward M. ;

Kornepati, Anand V. R. ;

Sousa, Alexander ;

Collins, McKensie A. ;

Jayaram, Hari ;

Cullen, Bryan R. ;

Bumcrot, David .

GENOME BIOLOGY, 2015, 16

[7] Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways [J].

Goodwin, EC ;

DiMaio, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12513-12518

[8] Primary tumour genetic alterations and intra-tumoral heterogeneity are maintained in xenografts of human colon cancers showing chromosome instability [J].

Guenot, D ;

Guérin, E ;

Aguillon-Romain, S ;

Pencreach, E ;

Schneider, A ;

Neuville, A ;

Chenard, MP ;

Duluc, I ;

Du Manoir, S ;

Brigand, C ;

Oudet, P ;

Kedinger, M ;

Gaub, MP .

JOURNAL OF PATHOLOGY, 2006, 208 (05) :643-652

[9] Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin [J].

Gunderson, Leonard L. ;

Winter, Kathryn A. ;

Ajani, Jaffer A. ;

Pedersen, John E. ;

Moughan, Jennifer ;

Benson, Al B., III ;

Thomas, Charles R., Jr. ;

Mayer, Robert J. ;

Haddock, Michael G. ;

Rich, Tyvin A. ;

Willett, Christopher G. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (35) :4344-4351

[10]

HOWLEY PM, 1991, CANCER RES, V51, pS5019

← 1 2 3 →