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Focal Gene Delivery in the Lymphedema Murine Tail Model Using Tissue Nanotransfection Technology (TNT)
Ganesh Mohan, Imran Khan, Mithun Sinha, Gayle M. Gordillo, Chandan K. Sen, Aladdin H. Hassanein
University
2022-01-14
Presenter: Ganesh Mohan
Affidavit:
100% of the work in this project is the original work of the presenting and his cited colleagues.
Director Name: Aladdin Hassanein
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)
Introduction
Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects 5 million Americans and is most commonly breast cancer related. There is no cure for this disease. Experimental gene-based therapeutic approaches (e.g., using viral vectors) have had limited translational applicability. Tissue nanotransfection technology (TNT) utilizes a direct, transcutaneous non-viral vector, gene delivery using a chip with nanochannel poration in a rapid (<100ms) focused electric field. The purpose of this study is to experimentally evaluate the applicability of TNT for lymphedema.
Methods
Acquired lymphedema was surgically induced in the tails of C57BL/6 mice. TNT was applied to the murine tail (day 0) directly at the surgical site: Group I (control) was given pCMV6 (vector alone) (n=6); Group II had pCMV6-Prox1 (n=6). TNT was applied with a square wave pulse electric stimulation (10x10ms pulses, 250 V, 10 mA). The efficiency of gene delivery was assessed through qRT-PCR and immunostaining.
Results
The experimental Group II exhibited four-fold increased expression of Prox1 using qRT-PCR compared to control Group I at the site of TNT treatment (P=0.002). Increased expression of Prox1 was also observed with immunohistochemistry 3 days post-TNT application. Intensity quantification of immunohistochemistry revealed greater expression of Prox1 in Group II when compared to Group I (P=0.002).
Conclusion
This study demonstrates the ability to deliver genetic cargo at a focal, non-global site in the murine tail model by TNT. TNT can rapidly and effectively be applied for potentially therapeutic delivery of factors locally at the site of lymphedema.
