PhD Scientific Days 2017

Oral Presentations: Basic Sciences II.

Organ specific induction of lymphatic growth with nanoparticle-encapsulated nucleoside-modified VEGFC mRNA (VEGFC mRNA-LNP) complexes in vivo

Előadó neve

Styevkóné Dinnyés, Andrea

Előadó munkahelye

Department of Physiology, Semmelweis University School of Medicine and MTA-SE „Lendület” Lymphatic Physiology Research Group, Budapest, Hungary

Előadó telefonszáma

0614591500 x60454

Előadó e-mail címe

dinnyes.andrea@med.semmelweis-univ.hu

Az előadás címe

Organ specific induction of lymphatic growth with nanoparticle-encapsulated nucleoside-modified VEGFC mRNA (VEGFC mRNA-LNP) complexes in vivo

Szerző(k) neve és munkahelye

Andrea Styevkóné Dinnyés1, Dániel Szőke1, Norbert Pardi2, Kitti Ajtay1, Drew Weissman2, Zoltán Jakus1
1 Department of Physiology, Semmelweis University School of Medicine and MTA-SE „Lendület” Lymphatic Physiology Research Group, Budapest, Hungary
2 University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

Témacsoport

molecular sciences

Szekció

Oral Presentations: Basic Sciences II.

Data of the presenter

Doctoral School of Molecular Medicine
Cellular and Molecular Physiology
Zoltán Jakus MD, PhD
jakus.zoltan@med.semmelweis-univ.hu

Text of the abstract

Introduction: Lack or malfunction of lymphatics leads to the development of primary or secondary lymphedema. Currently, there is no efficient therapeutic approach for restoring lymphatic function in these diseases.

Aims: We aimed to develop a novel nanoparticle-encapsulated nucleoside-modified VEGFC mRNA complex (VEGFC mRNA-LNP) based system to induce lymphatic growth in vivo.

Methods: In our experiments purified nucleoside-modified mRNA (full-length VEGFC, GFP and poly(C) mRNA) were encapsulated into lipid nanoparticles. To characterize the system cell lines were transfected with mRNA-LNP complexes in vitro, and protein expression levels were monitored. Wild type and lymphatic reporter animals were injected with mRNA-LNPs locally or systemically, and lymphatic growth was assessed.

Results: We found that GFP and VEGFC mRNA-LNP complex transfection results in protein expression in cell lines in vitro. After injecting GFP mRNA-LNP complexes, significant increase of fluorescent signal was detected in isolated organs in vivo. Furthermore, we detected increased lymphatic growth after organ specific VEGFC mRNA-LNP treatment of the skin, diaphragm and skeletal muscle etc. with significant increase in the length, diameter and branch points of the lymphatic vessels.

Conclusions: Our results indicate that the mRNA-LNP system is an effective approach to trigger protein expression in vitro and in vivo. Furthermore, expression of VEGFC mRNA-LNP complexes is an efficient tool to induce lymphatic growth, which is a novel gain of function model to assess the organ specific physiological and pathophysiological roles of the lymphatic system. In addition, the system may provide the basis for the development of a new therapeutic tool for the treatment of lymphedemas in the future.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1323

Authors (legacy)

Andrea Styevkóné Dinnyés1, Dániel Szőke1, Norbert Pardi2, Kitti Ajtay1, Drew Weissman2, Zoltán Jakus1
1 Department of Physiology, Semmelweis University School of Medicine and MTA-SE „Lendület” Lymphatic Physiology Research Group, Budapest, Hungary
2 University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA