Related Experiment Video
Updated: Mar 11, 2026
Author Spotlight: Modeling Brain Tumors In Vivo Using Electroporation-Based Delivery of Plasmid DNA Representing Patient Mutation Signatures
Published on: June 23, 2023
APOBEC3A intratumoral DNA electroporation in mice
A Kostrzak1, V Caval2, M Escande1
1Invectys, Pepinière Paris Biotech Santé Cochin, Paris, France.
Abstract:
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-A*0201/DRB1*0101 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.
Insights
Human APOBEC3A (A3A) gene therapy showed potential in treating small melanoma tumors in mice. Larger tumors were less responsive, suggesting A3A may be more effective in human cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Immunology
Background:
- Human APOBEC3A (A3A) is a cytidine deaminase with known pro-apoptotic effects.
- A3A induces genomic DNA hypermutation, double-stranded DNA breaks (DSBs), and G1 cell cycle arrest.
Purpose of the Study:
- To evaluate the antitumor efficacy of A3A delivered via intratumoral electroporation.
- To assess A3A's effectiveness in different mouse tumor models.
Main Methods:
- Intratumoral electroporation of an A3A expression plasmid into B16OVA, B16Luc, and Sarc2 tumors in mice.
- Utilized noninvasive plate electrodes for repeated DNA delivery.
Main Results:
- Intratumoral A3A electroporation led to the regression of approximately 50% of small B16OVA melanoma tumors.
- Larger or more aggressive tumors showed resistance to A3A treatment.
- A3A demonstrated lower efficiency in inducing hypermutation and DSBs in mouse B16OVA cells compared to human or quail cells.
Conclusions:
- A3A gene therapy shows promise for treating certain types of tumors, particularly smaller melanomas.
- The efficacy of A3A may be greater in human applications than in current mouse models due to species-specific differences in cellular response.
