Development of a novel adenovirus–alphavirus hybrid vector with RNA replicon features for malignant hematopoietic cell transduction

作者: Y Yang , F Xiao , Z Lu , Z Li , H Zuo

DOI: 10.1038/CGT.2013.37

关键词: Hybrid vectorSemliki Forest virusK562 cellsBiologyLeukemiaMolecular biologyRepliconCell cultureJurkat cellsVirologyMultiplicity of infectionMolecular medicineCancer research

摘要: To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains Semliki Forest Virus (SFV) replicon and chimeric fibers Ad5 Ad11p. infected >95% K562, U937 or Jurkat cells 23.65% HL-60 led to moderate Enhanced Green Fluorescent Protein (EGFP) transgene intensity. The infection efficiency primary human leukemia ranged from 9.34-89.63% (median, 28.58%) at multiplicity (MOI) 100, compared with only 3.37-44.54% 10.42%) by Ad5/F11p-GFP. Importantly, significantly higher level as indicated relative fluorescence intensity, increased EGFP Ad5/F11p-SFV-GFP-infected was associated accumulation abundant subgenomic mRNA. Additionally, inhibited blocking CD46 receptor; however, other factors may affect gene-transfer cells. In conclusion, successfully RNA features, which represents promising for gene modifications during production cell-based vaccines patients.

参考文章(27)
Céline Rhême, Markus U. Ehrengruber, Denis Grandgirard, Alphaviral cytotoxicity and its implication in vector development. Experimental Physiology. ,vol. 90, pp. 45- 52 ,(2005) , 10.1113/EXPPHYSIOL.2004.028142
Karl Seeger, Manuel Schmidt, Burghardt Wittig, Hagen G. von Einsiedel, Florian Sack, Günter Henze, Sven A. König-Merediz, Dirk Buchwald, Renata Stripecke, Alexander Korte, Joachim Köchling, Protection of mice against Philadelphia chromosome-positive acute lymphoblastic leukemia by cell-based vaccination using nonviral, minimalistic expression vectors and immunomodulatory oligonucleotides. Clinical Cancer Research. ,vol. 9, pp. 3142- 3149 ,(2003)
Hongjie Wang, Zong-Yi Li, Ying Liu, Jonas Persson, Ines Beyer, Thomas Möller, Dilara Koyuncu, Max R Drescher, Robert Strauss, Xiao-Bing Zhang, James K Wahl, Nicole Urban, Charles Drescher, Akseli Hemminki, Pascal Fender, André Lieber, Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14 Nature Medicine. ,vol. 17, pp. 96- 104 ,(2011) , 10.1038/NM.2270
Erkuden Casales, Alejandro Aranda, Jose I. Quetglas, Marta Ruiz-Guillen, Juan R. Rodriguez-Madoz, Jesus Prieto, Cristian Smerdou, A novel system for the production of high levels of functional human therapeutic proteins in stable cells with a Semliki Forest virus noncytopathic vector. New Biotechnology. ,vol. 27, pp. 138- 148 ,(2010) , 10.1016/J.NBT.2010.02.005
R. D. Cornwell, K. A. Gollahon, D. D. Hickstein, Description of the leukocyte function-associated antigen 1 (LFA-1 or CD11a) promoter. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 4221- 4225 ,(1993) , 10.1073/PNAS.90.9.4221
Yuan Sun, Hong-Yu Li, Da-Yong Tian, Qiu-Ying Han, Xin Zhang, Na Li, Hua-Ji Qiu, A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces sterile immunity against classical swine fever Vaccine. ,vol. 29, pp. 8364- 8372 ,(2011) , 10.1016/J.VACCINE.2011.08.085
Min Guan, Juan R. Rodriguez-Madoz, Pilar Alzuguren, Celia Gomar, M. Gabriela Kramer, Stefan Kochanek, Jesus Prieto, Cristian Smerdou, Cheng Qian, Increased Efficacy and Safety in the Treatment of Experimental Liver Cancer with a Novel Adenovirus-Alphavirus Hybrid Vector Cancer Research. ,vol. 66, pp. 1620- 1629 ,(2006) , 10.1158/0008-5472.CAN-05-0877
Aurore Saudemont, Selim Corm, Thomas Wickham, Dominique Hetuin, Bruno Quesnel, Induction of leukemia-specific CD8+ cytotoxic t cells with autologous myeloid leukemic cells maturated with a fiber-modified adenovirus encoding TNF-α Molecular Therapy. ,vol. 11, pp. 950- 959 ,(2005) , 10.1016/J.YMTHE.2004.12.016
Hyoung Jin Kang, Cynthia C Bartholomae, Anna Paruzynski, Anne Arens, Sujeong Kim, Seung Shin Yu, Youngtae Hong, Chang-Wan Joo, Nam-Kyung Yoon, Jung-Woo Rhim, Joong Gon Kim, Christof Von Kalle, Manfred Schmidt, Sunyoung Kim, Hyo Seop Ahn, Retroviral Gene Therapy for X-linked Chronic Granulomatous Disease: Results From Phase I/II Trial Molecular Therapy. ,vol. 19, pp. 2092- 2101 ,(2011) , 10.1038/MT.2011.166