2010 Fiscal Year Final Research Report
Development of sarcoma-targeting agents utilizing viral engineering
Project/Area Number |
20591772
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses |
Principal Investigator |
YAMAMURA Hisako Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses, 研究所, 研究員 (50342994)
|
Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsuhito 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 部長 (40211338)
|
Project Period (FY) |
2008 – 2010
|
Keywords | 肉腫 / 腫瘍溶解性ウイルス / 標的遺伝子療法 |
Research Abstract |
Toward the development of a novel therapeutic strategy for sarcoma, the purpose of this study is to develop a novel procedure for purification of oncolytic viral seed stock with homogeneous viral genome DNA. Single viral geneome DNA was cloned into BACmid and was purified from HSV-1 oncolytic viruses, d12.CALPfΔRR targeting calponin-expressing sarcoma and d12ODDΔRR targeting hypoxic microenvironment of tumor. The BACmid containing clonal viral genome was transformed into E. Coli, maxi-prep'ed and sequencesed. No mutation, even in the single nucleotide was detected in the sequence of Thimidine kinase gene through cloning into BACmid and preparation in E. Coli. d12.CALPfΔRR and d12ODDΔRR viruses without BACmid sequence were purified by limited dilution methods. We confirmed that the purified d12ODDΔRR virus destroyed stem (tumot-initiating) cell fraction of sarcomatous mesothelioma, and also effective for destruction of cultured leiomyosarcoma cells which were established from tumors resistant to both chemotherapy- and molecular targeted therapy.
|
Research Products
(14 results)