APOBEC3A intratumoral DNA electroporation in mice

Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression pla...

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Bibliographic Details
Published in:	Gene therapy Vol. 24; no. 2; pp. 74 - 83
Main Authors:	Kostrzak, A, Caval, V, Escande, M, Pliquet, E, Thalmensi, J, Bestetti, T, Julithe, M, Fiette, L, Huet, T, Wain-Hobson, S, Langlade-Demoyen, P
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-02-2017 Nature Publishing Group
Subjects:	13/106 13/51 45/77 59/5 631/1647/1407 631/1647/1511 631/45/607/1164 631/67/1059 631/67/1813/1634 64/60 Analysis Animals Antitumor activity Apolipoproteins Apoptosis Biochemistry, Molecular Biology Biomedical and Life Sciences Biomedicine Biotechnology Care and treatment Cell Biology Cell cycle Cytidine deaminase Cytidine Deaminase - genetics Deoxyribonucleic acid Diagnosis DNA DNA damage Drb1 protein Electroporation Electroporation - methods Female Fibrosarcoma Gene Expression Gene mutation Gene Therapy Genes Genetic engineering Genetic Therapy Histocompatibility antigens HLA histocompatibility antigens Human Genetics Life Sciences Lymphocytes, Tumor-Infiltrating - immunology Male Melanoma Melanoma, Experimental - genetics Melanoma, Experimental - immunology Melanoma, Experimental - therapy Methods Mice Mice, Inbred C57BL Molecular biology Mutation Nanotechnology original-article Plasmids - genetics Proteins - genetics Risk factors Testing Transgenic mice Tumor Cells, Cultured Tumors France Cytological techniques Hydrolases Genetic engineering Cancer therapy Melanoma
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Summary:	Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A0201/DRB10101 transgenic mice using noninvasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors that did not rebound in the following 2 months without treatment. Larger or more aggressive tumors escaped regression when so treated. As APOBEC3A was much less efficient in provoking hypermutation and DSBs in B16OVA cells compared with human or quail cells, it is likely that APOBEC3A would be more efficient in a human setting than in a mouse model.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0969-7128 1476-5462
DOI:	10.1038/gt.2016.77