报告题目：Targeted delivery of TGFβ mRNA to lung parenchyma using one-component Ionizable Amphiphilic Janus Dendrimers

报告人：Dr. Elena Atochina-Vasserman, Assistant Professor at the University of Pennsylvania

时间：2024年7月2日（周二） 9:30-11:00

地点：商学院216

邀请人：李永生 教授，张大朋 教授

个人简介：

Dr. Elena Atochina-Vasserman is a Research Assistant Professor of Medicine at the Penn Institute of RNA Innovation at the University of Pennsylvania. Elena’s expertise in the targeted delivery of mRNA therapeutics to the lungs plays a crucial role in treating pulmonary diseases. Dr. Elena Atochina-Vasserman has contributed significantly to the field with over 100 published papers and several patents. Dr. Atochina-Vasserman earned her M.D. from Tomsk Medical School and a Ph.D. from the Cardiology Research Center in Moscow, Russia. Elena’s early research concentrated on the targeted delivery of therapeutics to the pulmonary angiotensin-converting enzyme. Elena further continued to advance in understanding and treatment of pulmonary diseases.

Dr. Atochina-Vasserman now is a group member of Dr. Drew Weissman (The Nobel Prize in Physiology or Medicine 2023), marking a pivotal expansion of her research into the development of novel mRNA-based therapeutic delivery systems targeting the lung. Elena's innovative approach to research has led to a collaboration with Dr. Virgil Percec at the Department of Chemistry. Together, they have been instrumental in developing single-component particles, notably ionizable amphiphilic Janus dendrimers.  This innovative approach serves as a promising alternative to the traditional four-component lipid nanoparticle (LNP) systems and has the potential to revolutionize the delivery of mRNA therapeutics and offering new avenues for treating pulmonary diseases.

报告摘要：

Acute lung injury (ALI), diagnosed in nearly 200,000 individuals annually, is associated with a high rate of morbidity and mortality. Treatments for ALI are limited partly due to an ability to deliver treatments to the lung parenchyma, ALI's primary site. This study explores one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a vehicle to deliver anti-inflammatory cytokines. Specifically, we used TGFb mRNA to deliver transient anti-inflammatory expression to the lung parenchyma. Various doses of TGFβ mRNA, formulated with IAJD34, were administrated to mice via retro-orbital injections. Mice were euthanized 24 hours post-injections, and lung, liver, spleen, and kidney tissues were collected for further analysis. The collected tissues were stained with hematoxylin and eosin and evaluated for histopathological alterations. Lung tissue was also immunohistochemically stained for TGFβ or IgG control to confirm TGFβ protein expression. Delivering 10 µg/mouse of TGFβ mRNA resulted in diffuse TGFβ protein expression within the lung parenchyma. Additionally, we observed no toxicity in the liver, spleen, or kidney, with some non-significant increases in fibrin deposition in the lung at a high dose of 30 mg/mouse. This study highlights IAJD34’s potential for precise, effective delivery of TGFβ mRNA to the lung parenchyma, offering a promising approach for treatment of ALI.