Accelerating CAR T Cell Therapy: Lipid Nanoparticles Speed Up Manufacturing

by Ian Scheffler

Visualization of a CAR T cell (in red) attacking a cancer cell (in blue) (Meletios Varras via Getty Images)

For patients with certain types of cancer, CAR T cell therapy has been nothing short of life changing. Developed in part by Carl June, Richard W. Vague Professor at Penn Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.

However, the process for manufacturing CAR T cells themselves is time-consuming and costly, requiring multiple steps across days. The state of the art involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.

Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step, thanks to the use of lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.

In a new paper in Advanced Materials, Michael J. Mitchell, Associate Professor in Bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying  the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student in Bioengineering and NSF Graduate Research Fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”

Read the full story in Penn Engineering Today.

Precision Pulmonary Medicine: Penn Engineers Target Lung Disease with Lipid Nanoparticles

by Ian Scheffler

Penn Engineers have developed a way to target lung diseases, including lung cancer, with lipid nanoparticles (LNPs). (wildpixel via Getty Images)

Penn Engineers have developed a new means of targeting the lungs with lipid nanoparticles (LNPs), the miniscule capsules used by the Moderna and Pfizer-BioNTech COVID-19 vaccines to deliver mRNA, opening the door to novel treatments for pulmonary diseases like cystic fibrosis. 

In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, demonstrates a new method for efficiently determining which LNPs are likely to bind to the lungs, rather than the liver. “The way the liver is designed,” says Mitchell, “LNPs tend to filter into hepatic cells, and struggle to arrive anywhere else. Being able to target the lungs is potentially life-changing for someone with lung cancer or cystic fibrosis.”

Previous studies have shown that cationic lipids — lipids that are positively charged — are more likely to successfully deliver their contents to lung tissue. “However, the commercial cationic lipids are usually highly positively charged and toxic,” says Lulu Xue, a postdoctoral fellow in the Mitchell Lab and the paper’s first author. Since cell membranes are negatively charged, lipids with too strong a positive charge can literally rip apart target cells.  

Typically, it would require hundreds of mice to individually test the members of a “library” of LNPs — chemical variants with different structures and properties — to find one with a low charge that has a higher likelihood of delivering a medicinal payload to the lungs.

Instead, Xue, Mitchell and their collaborators used what is known as “barcoded DNA” (b-DNA) to tag each LNP with a unique strand of genetic material, so that they could inject a pool of LNPs into just a handful of animal models. Then, once the LNPs had propagated to different organs, the b-DNA could be scanned, like an item at the supermarket, to determine which LNPs wound up in the lungs. 

Read the full story in Penn Engineering Today.

A Moonshot for Obesity: New Molecules, Inspired by Space Shuttles, Advance Lipid Nanoparticle Delivery for Weight Control

by Ian Scheffler

Like space shuttles using booster rockets to breach the atmosphere, lipid nanoparticles (LNPs) equipped with the new molecule more successfully deliver medicinal payloads. (Love Employee via Getty Images)

Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.

In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. For this paper, Mitchell and his co-authors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease. 

Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA to cells, but the methods for creating these molecules are time- and cost-intensive. “We offer a novel construction strategy for rapid and cost-efficient synthesis of these lipidoids,” says Xuexiang Han, a postdoctoral student in the Mitchell Lab and the paper’s co-first author. 

Read the full story in Penn Engineering Today.

What Makes a Breakthrough? “Eight Steps Back” Before Making it to the Finish Lit

by Meagan Raeke

(From left to right) Breakthrough Prize recipients Drew Weissman, Virginia M-Y Lee, Katalin Karikó, and Carl June at a reception on Feb. 13. (Image: Courtesy of Penn Medicine News)

In popular culture, scientific discovery is often portrayed in “Eureka!” moments of sudden realization: a lightbulb moment, coming sometimes by accident. But in real life—and in Penn Medicine’s rich history as a scientific innovator for more than 250 years—scientific breakthroughs can never truly be distilled down to a single, “ah-ha” moment. They’re the result of years of hard work, perseverance, and determination to keep going, despite repeated, often discouraging, barriers and setbacks. 

“Research is [like taking], four, or six, or eight steps back, and then a little stumble forward,” said Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research. “You keep doing that over and over and somehow, rarely, you can get to the top of the step.” 

For Weissman and his research partner, Katalin Karikó, PhD, an adjunct professor of Neurosurgery, that persistence—documented in thousands of news stories across the globe—led to the mRNA technology that enabled two lifesaving COVID-19 vaccines, earning the duo numerous accolades, including the highest scientific honor, the 2023 Nobel Prize in Medicine

Weissman and Karikó were also the 2022 recipients of the Breakthrough Prize in Life Sciences, the world’s largest science awards, popularly known as the “Oscars of Science.” Founded in 2012 by a group of web and tech luminaries including Google co-founder Sergey Brin and Meta CEO Mark Zuckerberg, the Breakthrough Prizes recognize “the world’s top scientists working in the fundamental sciences—the disciplines that ask the biggest questions and find the deepest explanations.” With six total winners, including four from the Perelman School of Medicine (PSOM), Penn stands alongside Harvard and MIT as the institutions whose researchers have been honored with the most Breakthrough Prizes. 

Virginia M.Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research, was awarded the Prize in 2020 for discovering how different forms of misfolded proteins can move from cell to cell and lead to neurodegenerative disease progression. Carl June, MD, the Richard W. Vague Professor in Immunotherapy, is the most recent recipient and will be recognized at a star-studded red-carpet event in April for pioneering the development of CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.

The four PSOM Breakthrough Prize recipients were honored on Tuesday, Feb. 13, 2024, when a new large-scale installation was unveiled in the lobby of the Biomedical Research Building to celebrate each laurate and their life-changing discoveries. During a light-hearted panel discussion, the honorees shared how a clear purpose, dogged determination, and a good sense of humor enabled their momentum forward. 

Read the full story in Penn Medicine News.

Carl June and Jon Epstein are members of the Penn Bioengineering Graduate Group. Read more stories featuring them in the BE Blog here and here, respectively.

Weissman presented the Department of Bioengineering’s 2022 Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics.” Read more stories featuring Weissman in the BE Blog here.

How Penn Medicine Is Changing the World with mRNA

by Rachel Ewing

Vaccines for COVID-19 were the first time that mRNA technology was used to address a worldwide health challenge. The Penn Medicine scientists behind that technology were awarded the 2023 Nobel Prize in Physiology or Medicine. Next come all the rest of the potential new treatments made possible by their discoveries.

Starting in the late 1990s, working together at Penn Medicine, Katalin Karikó, PhD, and Drew Weissman, MD, PhD, discovered how to safely use messenger RNA (mRNA) as a whole new type of vaccine or therapy for diseases. When the COVID-19 pandemic hit in 2020, these discoveries made Pfizer/BioNTech and Moderna’s new vaccines possible—saving millions of lives. 

But curbing the pandemic was only the beginning of the potential for this Nobel Prize-winning technology. 

These biomedical innovations from Penn Medicine in using mRNA represent a multi-use tool, not just a treatment for a single disease. The technology’s potential is virtually unlimited; if researchers know the sequence of a particular protein they want to create or replace, it should be possible to target a specific disease. Through the Penn Institute for RNA Innovation led by Weissman, who is the Roberts Family Professor of Vaccine Research in Penn’s Perelman School of Medicine, researchers are working to ensure this limitless potential meets the world’s most challenging and important needs.

Infectious Diseases and Beyond

Just consider some of the many projects Weissman’s lab is partnering in: “We’re working on malaria with people across the U.S. and in Africa,” Weissman said. “We’re working on leptospirosis with people in Southeast Asia. We’re working on vaccines for peanut allergies. We’re working on vaccines for autoimmunity. And all of this is through collaboration.”

Clinical trials are underway for the new malaria vaccine, as well as for a Penn-developed mRNA vaccine for genital herpes and one that aims to protect against all varieties of coronaviruses. Trials should begin soon for vaccines for norovirus and the bacterium C. difficile.

Single-Injection Gene Therapies for Sickle Cell and Heart Disease

Drew Weissman, MD, PhD, is a co-winner of the 2023 Nobel Prize in Physiology or Medicine for discoveries with mRNA.

The Weissman lab is working to deploy mRNA technology as an accessible gene therapy for sickle cell anemia, a devastating and painful genetic disease that affects about 20 million people around the world. About 300,000 babies are born each year with the condition, mainly in sub-Saharan Africa. Weissman’s team has developed technology to efficiently deliver modified mRNA to bone marrow stem cells, instructing red blood cells to produce normal hemoglobin instead of the malformed “sickle” version that causes the illness. Conventional gene therapies are complex and expensive treatments, but the mRNA gene therapy could be a simple, one-time intravenous injection to cure the disease. Such a treatment would have applications to many other congenital gene defects in blood and stem cells.

In another new program, Penn Medicine researchers have found a way to target the muscle cells of the heart. This gene therapy method developed by Weissman’s team, together with Vlad Muzykantov, MD, PhD, the Founders Professor in Nanoparticle Research could potentially repair the heart or increase blood flow to the heart, noninvasively, after a heart attack or to correct a genetic deficiency in the heart. “That is important because heart disease is the number one killer in the U.S. and in the world,” Weissman said. “Drugs for heart disease aren’t specific for the heart. And when you’re trying to treat a myocardial infarction or cardiomyopathy or other genetic deficiencies in the heart, it’s very difficult, because you can’t deliver to the heart.”

Weissman’s team also is partnering on programs for neurodevelopmental diseases and for neurodegenerative diseases, to replace genes or deliver therapeutic proteins that will treat and potentially cure these diseases.

“The potential is unbelievable,” Weissman said. “We haven’t thought of everything that can be done.”

Read the full story in Penn Medicine News.

Vladimir R. Muzykantov is Founders Professor in Nanoparticle Research in the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

The Future of Medicine Rises in University City: University of Pennsylvania Opens New Multi-Disciplinary Research Labs in One uCity Square

by Holly Wojcik

One uCity Square

On September 14, Wexford Science & Technology, LLC and the University of Pennsylvania announced that the University has signed a lease for new laboratory space that will usher in a wave of novel vaccine, therapeutics, and engineered diagnostics research to West Philadelphia. Research teams from Penn are poised to move into 115,000 square feet of space at One uCity Square, the 13-story, 400,000 square foot purpose-built lab and office building within the vibrant uCity Square Knowledge Community being developed by Wexford. This is the largest lease in the building, encompassing four floors, and bringing the building to over 90% leased. The building currently includes industry tenants Century Therapeutics (NASDAQ: IPSC), Integral Molecular, Exponent (NASDAQ: EXPO), and Charles River Laboratories (NYSE: CRL).

The new University space will house Penn Medicine’s Institute for RNA Innovation and Penn Engineering’s Center for Precision Engineering for Health, underscoring the University’s commitment to a multi-disciplinary and collaborative approach to research that will attract and retain the best talent and engage partners from across the region. Penn’s decision to locate at One uCity Square reinforces uCity Square’s evolution as a central cluster of academic, clinical, commercial, entrepreneurial, and amenity spaces for the area’s innovation ecosystem, and further cements Philadelphia’s position as a top life sciences market.

Jonathan Epstein, MD, Executive Vice Dean and Chief Scientific Officer of Penn Medicine, shared his anticipation for the opportunities that lie ahead: “Penn Medicine is proud to build on its existing clinical presence in uCity Square and establish an innovative and collaborative research presence at the heart of uCity Square’s multidisciplinary innovation ecosystem. This strategic move underscores our commitment to accelerating advancements in biomedical research, industry collaboration, and equipping our talented teams with the resources they need to shape the future of healthcare.”

Locating the Penn Institute for RNA Innovation in the heart of the uCity Square community brings together researchers across disciplines who are already pursuing new vaccines and treatments, and better ways to deliver them. Their shared work will help to power the next phase of vaccine discovery and development.

Likewise, anchoring the work of Penn Engineering’s Center in the One uCity Square space will allow the School’s multi-disciplinary researchers and their collaborators to advance new clinical and diagnostic methods that will focus on intelligent therapeutics, genome design, diagnostics for discovery of human biology, and engineering the human immune shield.

“Penn Engineering has made a substantial commitment to precision engineering for health, an area that is not only important and relevant to engineering, but also critical to the future of humanity,” said Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “The space in One uCity Square will add another 30,000 square feet of space for our engineers to develop technologies that will fight future pandemics, cure incurable diseases, and extend healthy life spans around the world.”

Spearheading the Penn Institute for RNA Innovation will be Drew Weissman, MD, PhD, the Roberts Family Professor for Vaccine Research, who along with Katalin Karikó, PhD, adjunct professor of Neurosurgery, discovered foundational mRNA technology that enabled the creation of vital vaccine technology, including the FDA-approved mRNA-based COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.

In this new space at One uCity Square, Weissman and his research team and collaborators will further pursue their groundbreaking research efforts with a goal to develop new therapeutics and vaccines and initiate clinical trials for other devastating diseases.

In addition, two established researchers will join the Institute at One uCity Square: Harvey Friedman, MD, a professor of Infectious Diseases, who leads a team researching various vaccines. He will be joined by Vladimir Muzykantov, MD, PhD, Founders Professor in Nanoparticle Research, who focuses on several projects related to targeting the delivery of drugs, including mRNA, to create more effective, targeted pathways to deliver drugs to the vascular system, treating a wide range of diseases that impact the brain, lung, heart, and blood.

Dan Hammer, Alfred G. and Meta A. Ennis Professor in the Departments of Bioengineering and Chemical and Biomolecular Engineering in Penn Engineering and Director of the Center for Precision Engineering for Health, will oversee the Center’s innovations in diagnostics and delivery, cellular and tissue engineering, and the development of new devices that integrate novel materials with human tissues. The Center will bring together scholars from all departments within Penn Engineering and will help to foster increased collaboration with campus colleagues at Penn’s Perelman School of Medicine and with industry partners.

Joining the Center researchers in One uCity Square are Noor Momin, Sherry Gao, and Michael Mitchell. Noor Momin, who will join Penn Engineering in early 2024 as an assistant professor in Bioengineering, will leverage her lab’s expertise in cardiovascular immunology, protein engineering and pharmacokinetic modeling to develop next-generation treatments and diagnostics for cardiovascular diseases.

Read the full story in Penn Engineering Today.

Jonathan Epstein and Vladimir Muzykantov are members of the Penn Bioengineering Graduate Group.

Michael Mitchell is an Associate Professor in Bioengineering.

An Improved Delivery System for mRNA Vaccines Provides More Powerful Protection

by Devorah Fischler

(From left to right) Xuexiang Han, Michael Mitchell and Mohamad-Gabriel Alameh

The COVID-19 vaccine swiftly undercut the worst of the pandemic for hundreds of millions around the world. Available sooner than almost anyone expected, these vaccines were a triumph of resourcefulness and skill.

Messenger RNA vaccines, like the ones manufactured by Moderna or Pfizer/BioNTech, owed their speed and success to decades of research reinforcing the safety and effectiveness of their unique immune-instructive technology.

Now, researchers from the University of Pennsylvania School of Engineering and Applied Science and the Perelman School of Medicine are refining the COVID-19 vaccine, creating an innovative delivery system for even more robust protection against the virus.

In addition to outlining a more flexible and effective COVID-19 vaccine, this work has potential to increase the scope of mRNA vaccines writ large, contributing to prevention and treatment for a range of different illnesses.

Michael Mitchell, associate professor in Penn Engineering’s Department of Bioengineering, Xuexiang Han, postdoctoral fellow in Mitchell’s lab, and Mohamad-Gabriel Alameh, postdoctoral fellow in Drew Weissman’s lab at Penn Medicine and incoming assistant professor in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine, recently published their findings in Nature Nanotechnology.

mRNA, or messenger ribonucleic acid, is the body’s natural go-between. mRNA contains the instructions our cells need to produce proteins that play important roles in our bodies’ health, including mounting immune responses.

The COVID-19 vaccines follow suit, sending a single strand of RNA to teach our cells how to recognize and fight the virus.

Read the full story in Penn Engineering Today.

2023 Graduate Research Fellowships for Bioengineering Students

Congratulations to the fourteen Bioengineering students to receive 2023  National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The recipients honorees were selected from a highly-competitive, nationwide pool. Further information about the program can be found on the NSF website.

Carlos Armando Aguila, Ph.D. student in Bioengineering, is a member of the Center of Neuroengineering and Therapeutics, advised by Erin Conrad, Assistant Professor in Neurology, and Brian Litt, Professor in Bioengineering and Neurology. His research focuses on analyzing electroencephalogram (EEG) signals to better understand epilepsy.

Joseph Lance Victoria Casila is a Ph.D. student in Bioengineering in the lab of Riccardo Gottardi, Assistant Professor in Pediatrics and Bioengineering. His research focuses on probing environmental factors that influence stem cell differentiation towards chondrogenesis for cartilage engineering and regeneration.

Trevor Chan is a Ph.D. student in Bioengineering in the lab of Felix Wehrli, Professor of Radiologic Science. His research is in developing computational methods for medical image refinement and analysis. Two ongoing projects are: self-supervised methods for CT super-resolution and assessment of osteoporosis, and semi-supervised segmentation of 3D and 4D echocardiograms for surgical correction of congenital heart-valve defects.

Rakan El-Mayta is an incoming Ph.D. student in the lab of Drew Weissman, Roberts Family Professor in Vaccine Research. Rakan studies messenger RNA-lipid nanoparticle vaccines for the treatment and prevention of infectious diseases. Prior to starting in the Bioengineering graduate program, he worked as a Research Assistant in Weissman lab and in the lab of Michael Mitchell, Associate Professor in Bioengineering.

Austin Jenk is a Ph.D. student in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering. Austin aims to develop early intervention, intra-articular therapeutics to combat the onset of post-traumatic osteoarthritis following acute joint injuries. His work focuses on developing a therapeutic that can be employed not only in conventional healthcare settings, but also emergency and battlefield medicine.

Jiageng Liu is a Ph.D. student in the lab of Alex Hughes, Assistant Professor in Bioengineering. His work aims to precisely control the bio-physical/chemical properties of iPSC-derived organoids with advanced synthetic biology approaches to create functional replacement renal tissues.

Alexandra Neeser is a Ph.D. student in the lab of Leyuan Ma, Assistant Professor of Pathology and Laboratory Medicine. Her research focuses on solid tumor microenvironment delivery of therapeutics.

 

William Karl Selboe Ojemann, a Ph.D. Student in Bioengineering, is a member of the Center for Neuroengineering and Therapeutics directed by Brian Litt, Professor in Bioengineering and Neurology. His research is focused on developing improved neurostimulation therapies for epilepsy and other neurological disorders.

Savan Patel (BSE Class of 2023) conducted research in the lab of Michael Mitchell, Associate Professor in Bioengineering, where he worked to develop lipid nanoparticle formulations for immunotherapy and extrahepatic delivery of mRNA. He will be joining the Harvard-MIT HST MEMP Ph.D. program in the fall of 2023.

David E. Reynolds, a Ph.D. student in Bioengineering, is a member of the lab of Jina Ko, Assistant Professor in Bioengineering and Pathology and Laboratory Medicine. His research focuses on developing novel and translatable technologies to address currently intractable diagnostic challenges for precision medicine.

Andre Roots is a Ph.D. student in the lab of Christopher Madl, Assistant Professor in Materials Science and Engineering. His research focuses on the use of protein engineering techniques and an optimized 3D human skeletal muscle microtissue platform to study the effects of biophysical material properties on cells.

Emily Sharp, a second year Ph.D. student in Bioengineering, is a member of the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering, part of the McKay Orthopaedic Research Laboratories. Her research focuses on designing multi-functional biomaterials to enhance tissue repair, specifically intervertebral disc repair following herniation and discectomy.

Nat Thurlow is a Ph.D. student in the lab of Louis J. Soslowsky, Fairhill Professor in Orthopedic Surgery and Bioengineering. Their current work focuses on delineating the roles of collagens V and XI in tendon mechanics, fibril structure, and gene expression during tendon development and healing.

Maggie Wagner, Ph.D. student in Bioengineering, is a member in the labs of Josh Baxter, Assistant Professor of Orthopaedic Surgery, and Flavia Vitale, Assistant Professor in Neurology and Bioengineering. Her research focuses on the development of novel sensors to record and monitor muscle neuromechanics.

Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics” (Drew Weissman, Perelman School of Medicine)

We hope you will join us for the Spring 2022 Herman P. Schwan Distinguished Lecture by Dr. Drew Weissman, hosted by the Department of Bioengineering.

Date: Tuesday, March 29, 2022
Time: 3:30-5:00 PM
Location: Bodek Lounge, Houston Hall
Reception to follow
Zoom Link
Password: schwan22

Drew Weissman, M.D., Ph.D.

Speaker: Drew Weissman, M.D., Ph.D.
Roberts Family Professor in Vaccine Research, Department of Medicine
Perelman School of Medicine
University of Pennsylvania

Abstract:

Vaccines prevent 4-5 million deaths a year making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA was developed over 15 years ago and has become the darling of the COVID-19 pandemic with the first 2 FDA approved vaccines based on it. These vaccines show greater than 90% efficacy and outstanding safety in clinical use. The mechanism for the outstanding immune response induction are the prolonged production of antigen leading to continuous loading of germinal centers and the adjuvant effect of the LNPs, which selectively stimulate T follicular helper cells that drive germinal center responses. Vaccine against many pathogens, including HIV, HCV, HSV2, CMV, universal influenza, coronavirus variants, pancoronavirus, nipah, norovirus, malaria, TB, and many others are currently in development. Nucleoside-modified mRNA is also being developed for therapeutic protein delivery. Clinical trials with mRNA encoded monoclonal antibodies are underway and many other therapeutic or genetic deficient proteins are being developed. Finally, nucleoside-modified mRNA-LNPs are being developed and used for gene therapy. Cas9 knockout to treat transthyretin amyloidosis has shown success in phase 1 trials. We have developed the ability to target specific cells and organs, including lung, brain, heart, CD4+ cells, all T cells, and bone marrow stem cells, with LNPs allowing specific delivery of gene editing and insertion systems to treat diseases such as sickle cell anemia, Nucleoside-modified mRNA will have an enormous potential in the development of new medical therapies.

Bio:

Drew Weissman, M.D., Ph.D. is a professor of Medicine at the Perelman School of Medicine, University of Pennsylvania. He received his graduate degrees from Boston University School of Medicine. Dr. Weissman, in collaboration with Dr. Katalin Karikó, discovered the ability of modified nucleosides in RNA to suppress activation of innate immune sensors and increase the translation of mRNA containing certain modified nucleosides. The nucleoside-modified mRNA-lipid nanoparticle vaccine platform Dr. Weissman’s lab created is used in the first 2 approved COVID-19 vaccines by Pfizer/BioNTech and Moderna. They continue to develop other vaccines that induce potent antibody and T cell responses with mRNA–based vaccines. Dr. Weissman’s lab also develops methods to replace genetically deficient proteins, edit the genome, and specifically target cells and organs with mRNA-LNPs, including lung, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells.

About the Schwan Lecture:

The Herman P. Schwan Distinguished Lecture is in honor of one of the founding members of the Department of Bioengineering, who emigrated from Germany after World War II and helped create the field of bioengineering in the US. It recognizes people with a similar transformative impact on the field of bioengineering.

Penn Engineers Secure Wellcome Leap Contract for Lipid Nanoparticle Research Essential in Delivery of RNA Therapies

by Melissa Pappas

The Very Large Scale Microfluidic Integration (VLSMI) platform, a technology developed by the Penn researchers, contains hundreds of mixing channels for mass-producing mRNA-carrying lipid nanoparticles.

Penn Engineering secured a multi-million-dollar contract with Wellcome Leap under the organization’s $60 million RNA Readiness + Response (R3) program, which is jointly funded with the Coalition for Epidemic Preparedness Innovations (CEPI). Penn Engineers aim to create “on-demand” manufacturing technology that can produce a range of RNA-based vaccines.

The Penn Engineering team features Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in Chemical and Biomolecular Engineering, Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, David Issadore, Associate Professor in Bioengineering and Electrical and Systems Engineering, and Sagar Yadavali, a former postdoctoral researcher in the Issadore and Lee labs and now the CEO of InfiniFluidics, a spinoff company based on their research. Drew Weissman of the Perelman School of Medicine, whose foundational research directly continued to the development of mRNA-based COVID-19 vaccines, is also a part of this interdisciplinary team.

The success of these COVID-19 vaccines has inspired a fresh perspective and wave of research funding for RNA therapeutics across a wide range of difficult diseases and health issues. These therapeutics now need to be equitably and efficiently distributed, something currently limited by the inefficient mRNA vaccine manufacturing processes which would rapidly translate technologies from the lab to the clinic.

Read more in Penn Engineering Today.