PhD Scientific Days 2020

Molecular Sciences V. Lectures

VEGFC mRNA-LNP Induces Organ-Specific Lymphatic Growth and Reverses Experimental Lymphedema

Előadó neve

Dr. Dániel, Szőke

Előadó munkahelye

Semmelweis University, Department of Physiology

Előadó telefonszáma

+36206701642

Előadó e-mail címe

szokedanielim@gmail.com

Az előadás címe

VEGFC mRNA-LNP Induces Organ-Specific Lymphatic Growth and Reverses Experimental Lymphedema

Szerző(k) neve és munkahelye

Dániel Szőke1,2, Gábor Kovács1,2, Éva Kemecsei1,2, László Bálint1,2, Kitti Ajtay1,2, Petra Aradi1,2,
Andrea Styevkóné Dinnyés1,2, Barbara L. Mui3, Ying K. Tam3, Thomas D. Madden3
, Katalin Karikó4, Raghu P. Kataru5, Michael J. Hope3, Drew Weissman6, Babak J. Mehrara5
, Norbert Pardi6,* and Zoltán Jakus1,2,*
1 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 MTA-SE „Lendület” Lymphatic Physiology Research Group of the Hungarian Academy of
Sciences and the Semmelweis University, Budapest, Hungary
3 Acuitas Therapeutics, Vancouver, BC, Canada
4 BioNTech RNA Pharmaceuticals, Mainz, Germany
5 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan
Kettering Cancer Center, New York, NY, USA
6 University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

Szekció

Molecular Sciences V. Lectures

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously
reduces the function of the affected organs and results in degradation of quality of life. Currently,
there is no definitive treatment option for lymphedema.
Our main goal is to show wether VEGFC mRNA-LNP induces lymphatic growth and could treat
lymphedema effectively in a mouse model.
Ears and other organs of Prox1-GFP transgenic mice were injected with Poly(C) – control – and VEGFC
mRNA-LNPs. The organs were harvested at various time points and examined by immunfluorescent
techniques. Lymphedema was induced in limbs of a Diphtheria Toxin based transgenic mouse model system. 8 days after the induction of lymphedema Poly(C) – control and VEGFC
mRNA-LNPs were injected into contralateral limbs of the animals. Thickness of the limbs were
measured and scored by two blinded investigators. The tissues were harvested at 30 and 75 days
after the treatment and examined by immunfluorescent techniques.
We utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine
Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and
reduce lymphedema in mouse models. We demonstrated that administration of a single low dose of
VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional
lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema
by restoring lymphatic function without inducing any obvious adverse events.
Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe
a model for identifying the organ-specific physiological and pathophysiological roles of the
lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic
tool to reduce lymphedema.

Additional Information

This work was supported by the Ministry of National Economy (EFOP-3.6.3-VEKOP-16-2017-00009).

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4768

Start

17:15

End

17:30

Authors (legacy)

Dániel Szőke1,2, Gábor Kovács1,2, Éva Kemecsei1,2, László Bálint1,2, Kitti Ajtay1,2, Petra Aradi1,2,
Andrea Styevkóné Dinnyés1,2, Barbara L. Mui3, Ying K. Tam3, Thomas D. Madden3
, Katalin Karikó4, Raghu P. Kataru5, Michael J. Hope3, Drew Weissman6, Babak J. Mehrara5
, Norbert Pardi6,* and Zoltán Jakus1,2,*
1 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 MTA-SE „Lendület” Lymphatic Physiology Research Group of the Hungarian Academy of
Sciences and the Semmelweis University, Budapest, Hungary
3 Acuitas Therapeutics, Vancouver, BC, Canada
4 BioNTech RNA Pharmaceuticals, Mainz, Germany
5 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan
Kettering Cancer Center, New York, NY, USA
6 University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA