The NSF AIRFoundry will accelerate RNA research using the power of AI and educate the next generation of RNA researchers. (DesignCells via Getty Images)
In a typical foundry, raw materials like steel and copper are melted down and poured into molds to assume new shapes and functions. The U.S. National Science Foundation Artificial Intelligence-driven RNA Foundry (NSF AIRFoundry), led by the University of Pennsylvania and the University of Puerto Rico and supported by an $18-million, six-year grant, will serve much the same purpose, only instead of smithing metal, the “BioFoundry” will create molecules and nanoparticles.
NSF AIRFoundry is one of five newly created BioFoundries, each of which will have a different focus. Bringing together researchers from Penn Engineering, Penn Medicine’s Institute for RNA Innovation, the University of Puerto Rico–Mayagüez (UPR-M), Drexel University, the Children’s Hospital of Philadelphia (CHOP) and InfiniFluidics, the facility, which will be physically located in West Philadelphia and at UPR-M, will focus on ribonucleic acid (RNA), the tiny molecule essential to genetic expression and protein synthesis that played a key role in the COVID-19 vaccines and saved tens of millions of lives.
The facility will use AI to design, optimize and synthesize RNA and delivery vehicles by augmenting human expertise, enabling rapid iterative experimentation, and providing predictive models and automated workflows to accelerate discovery and innovation.
“With NSF AIRFoundry, we are creating a hub for innovation in RNA technology that will empower scientists to tackle some of the world’s biggest challenges, from health care to environmental sustainability,” says Daeyeon Lee, Russell Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering in Penn Engineering and NSF AIRFoundry’s director.
“Our goal is to make cutting-edge RNA research accessible to a broad scientific community beyond the health care sector, accelerating basic research and discoveries that can lead to new treatments, improved crops and more resilient ecosystems,” adds Nobel laureate Drew Weissman, Roberts Family Professor in Vaccine Research in Penn Medicine, Director of the Penn Institute for RNA Innovation and NSF AIRFoundry’s senior associate director.
The facility will catalyze new innovations in the field by leveraging artificial intelligence (AI). AI has already shown great promise in drug discovery, poring over vast amounts of data to find hidden patterns. “By integrating artificial intelligence and advanced manufacturing techniques, the NSF AIRFoundry will revolutionize how we design and produce RNA-based solutions,” says David Issadore, Professor in Bioengineering and in Electrical and Systems Engineering at Penn Engineering and the facility’s associate director of research coordination.
Daeyeon Lee (left), Oren Friedman (center) and Sergei Vinogradov (right)
Each year, the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize, funded by Penn Health-Tech, awards $80,000 to a collaborative team of researchers from the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science for early-stage, interdisciplinary ideas.
This year, the NEMO Prize has been awarded to Penn Engineering’s Daeyeon Lee, Russel Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering, Oren Friedman, Associate Professor of Clinical Otorhinolaryngology in the Perelman School of Medicine, and Sergei Vinogradov, Professor in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Chemistry in the School of Arts & Sciences. Together, they are developing a new therapy that improves the survival and success of soft-tissue grafts used in reconstructive surgery.
More than one million people receive soft-tissue reconstructive surgery for reasons such as tissue trauma, cancer or birth defects. Autologous tissue transplants are those where cells and tissue such as fat, skin or cartilage are moved from one part of a patient’s body to another. As the tissue comes from the patient, there is little risk of transplant rejection. However, nearly one in four autologous transplants fail due to tissue hypoxia, or lack of oxygen. When transplants fail the only corrective option is more surgery. Many techniques have been proposed and even carried out to help oxygenate soft tissue before it is transplanted to avoid failures, but current solutions are time consuming and expensive. Some even have negative side effects. A new therapy to help oxygenate tissue quickly, safely and cost-effectively would not only increase successful outcomes of reconstructive surgery, but could be widely applied to other medical challenges.
The therapy proposed by this year’s NEMO Prize recipients is a conglomerate or polymer of microparticles that can encapsulate oxygen and disperse it in sustainable and controlled doses to specific locations over periods of time up to 72 hours. This gradual release of oxygen into the tissue from the time it is transplanted to the time it functionally reconnects to the body’s vascular system is essential to keeping the tissue alive.
“The microparticle design consists of an oxygenated core encapsulated in a polymer shell that enables the sustained release of oxygen from the particle,” says Lee. “The polymer composition and thickness can be controlled to optimize the release rate, making it adaptable to the needs of the hypoxic tissue.”
These life-saving particles are designed to be integrated into the tissue before transplantation. However, because they exist on the microscale, they can also be applied as a topical cream or injected into tissue after transplantation.
“Because the microparticles are applied directly into tissues topically or by interstitial injection (rather than being administered intravenously), they surpass the need for vascular channels to reach the hypoxic tissue,” says Friedman. “Their micron-scale size combined with their interstitial administration, minimizes the probability of diffusion away from the injury site or uptake into the circulatory system. The polymers we plan to use are FDA approved for sustained-release drug delivery, biocompatible and biodegrade within weeks in the body, presenting minimal risk of side effects.”
The research team is currently testing their technology in fat cells. Fat is an ideal first application because it is minimally invasive as an injectable filler, making it versatile in remodeling scars and healing injury sites. It is also the soft tissue type most prone to hypoxia during transplant surgeries, increasing the urgency for oxygenation therapy in this particular tissue type.
Daeyeon Lee, Professor and Evan C Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group, is the recipient of two recent honors.
Daeyeon Lee of the School of Engineering and Applied Science delivers the 2023 Thompson Chair Lecture on April 4, 2023. He spoke about reconnecting in the classroom and building community.
“Students who feel connected with instructors and among peers will invest more time, work harder, and retain information better, because they feel comfortable and safe being in the classroom and making space,” Lee said in his opening remarks. “So, there are clearly lots of positive benefits to having this connectedness among students in the classroom.”
Lee’s lecture, titled “(Re)connecting in the Classroom,” was inspired by the “Great Disengagement” referenced in an article published in The Chronicle of Higher Education last year. It portrayed students as more disconnected and uncertain as they re-entered the campus environment.
Read more about Lee’s “(Re)connecting in the Classroom” in Penn Today.
In addition, Lee has received the 2022 Outstanding Achievement Award in Nanoscience from the American Chemical Society (ACS).
The annual award recognizes exceptional achievements in nanoscience research and notable leadership in the area of colloidal nanoparticles and application. Lee was chosen from a large group of extraordinary nominees among the invited speakers, “for pioneering research in development of factory-on-a-chip and its application for large scale nanoparticle synthesis and functionalization.”
Dahin Song, a third year undergraduate student in Bioengineering, penned a guest blog post for Penn Career Services as part of their ongoing series of posts by recipients of the 2022 Career Services Summer Funding Grant. In this post, Song talks about her opportunity to conduct research in the SMART Lab of Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. During her summer research, Song worked on increasing the stability of the monolayer in microbubbles, gas particles which have been put to therapeutic use. She writes:
“My project was on increasing the stability of the monolayer using cholesterol; theoretically, this would decrease the permeability while maintaining the fluidity of the monolayer. Being given my own project at the get-go was initially intimidating; initial learning curve was overwhelming – along with new wet lab techniques and protocols, I learned a whole new topic well enough to ask meaningful questions. But in retrospect, throwing myself headlong into a project was the best method to immerse me in the research environment, especially as a first-time researcher. I learned how to read papers efficiently, troubleshoot research problems, navigate in a laboratory environment, and be comfortable with working independently but more importantly, with others.”
In a proof-of-concept study, researchers from the School of Dental Medicine and School of Engineering and Applied Science shows that a hands-free system could effectively automate the treatment and removal of tooth-decay-causing bacteria and dental plaque. (Illustration: Melissa Pappas)
A shapeshifting robotic microswarm may one day act as a toothbrush, rinse, and dental floss in one.
The technology, developed by a multidisciplinary team at the University of Pennsylvania, is poised to offer a new and automated way to perform the mundane but critical daily tasks of brushing and flossing. It’s a system that could be particularly valuable for those who lack the manual dexterity to clean their teeth effectively themselves.
The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss. In both instances, a catalytic reaction drives the nanoparticles to produce antimicrobials that kill harmful oral bacteria on site.
Experiments using this system on mock and real human teeth showed that the robotic assemblies can conform to a variety of shapes to nearly eliminate the sticky biofilms that lead to cavities and gum disease. The Penn team shared their findings establishing a proof-of-concept for the robotic system in the journal ACS Nano.
“Routine oral care is cumbersome and can pose challenges for many people, especially those who have hard time cleaning their teeth” says Hyun (Michel) Koo, a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn’s School of Dental Medicine and co-corresponding author on the study. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”
Hyun (Michel) Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in the School of Dental Medicine, co-director of the Center for Innovation & Precision Dentistry, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania.
Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.
Koo and Steager’s coauthors on the paper are Penn Dental Medicine’s Min Jun Oh, Alaa Babeer, Yuan Liu, and Zhi Ren and Penn Engineering’s Jingyu Wu, David A. Issadore, Kathleen J. Stebe, and Daeyeon Lee.
This work was supported in part by the National Institute for Dental and Craniofacial Research (grants DE025848 and DE029985), Procter & Gamble, and the Postdoctoral Research Program of Sungkyunkwan University.
Qazi obtained his Ph.D. at the Technical University of Berlin and the Charité Hospital in Berlin, Germany working on translational approaches for musculoskeletal tissue repair using biomaterials and stem cells under the co-advisement of Georg Duda, Director of the Berlin Institute of Health and David Mooney, Mercator Fellow at Charité – Universitätsmedizin Berlin. After arriving at Penn in 2019, Qazi performed research on microscale granular hydrogels in the Polymeric Biomaterials Laboratory of Jason Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. While conducting postdoctoral research, Qazi also collaborated with the groups of David Issadore, Associate Professor in Bioengineering and in Electrical and Systems Engineering, and Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. Qazi’s postdoctoral research was supported through a fellowship from the German Research Foundation, and resulted in several publications in high-profile journals, including Advanced Materials, Cell Stem Cell, Small, and ACS Biomaterials Science and Engineering.
“Taimoor has done really fantastic research as a postdoctoral fellow in the group,” says Burdick. “Purdue has a long history of excellence in biomaterials research and will be a great place for him to build a strong research program.”
Qazi’s future research program will engineer biomaterials to make fundamental and translational advances in musculoskeletal tissue engineering, including the study of how rare tissue-resident cells respond to spatiotemporal signals and participate in tissue repair, and developing modular hydrogels that permit minimally invasive delivery for tissue regeneration. The ultimate goal is to create scalable, translational, and biologically inspired healthcare solutions that benefit a patient population that is expected to grow manifold in the coming years.
Qazi is looking to build a strong and inclusive team of scientists and engineers with diverse backgrounds interested in tackling problems at the interface of translational medicine, materials science, bioengineering, and cell biology, and will be recruiting graduate students immediately. Interested students can contact him directly at thqazi@seas.upenn.edu.
“I am excited to launch my independent research career at a prestigious institution like Purdue,” says Qazi. “Being at Penn and particularly in the Department of Bioengineering greatly helped me prepare for the journey ahead. I am grateful for Jason’s mentorship over the years and the access to resources provided by Jason, Dave Issadore, Ravi, Dave Meany and other faculty which support the training and professional development of postdoctoral fellows in Penn Bioengineering.”
Congratulations to Dr. Qazi from everyone at Penn Bioengineering!
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.
COVID-19 vaccines are just the beginning for mRNA-based therapies; enabling a patient’s body to make almost any given protein could revolutionize care for other viruses, like HIV, as well as various cancers and genetic disorders. However, because mRNA molecules are very fragile, they require extremely low temperatures for storage and transportation. The logistical challenges and expense of maintaining these temperatures must be overcome before mRNA therapies can become truly widespread.
With these challenges in mind, Penn Engineering researchers are developing a new manufacturing technique that would be able to produce mRNA sequences on demand and on-site, isolating them in a way that removes the need for cryogenic temperatures. With more labs able to make and store mRNA-based therapeutics on their own, the “cold chain” between manufacturer and patient can be made shorter, faster and less expensive.
The National Science Foundation (NSF) is supporting this project, known as Distributed Ribonucleic Acid Manufacturing, or DReAM, through a four-year, $2 million grant from its Emerging Frontiers in Research and Innovation (EFRI) program.
The project will be led by Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in the Department of Chemical and Biomolecular Engineering (CBE), along with Kathleen Stebe, Richer and Elizabeth Goodwin Professor in CBE and in the Department of Mechanical Engineering and Applied Mechanics. They will collaborate with Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, Drexel University’s Masoud Soroush and Michael Grady, the University of Oklahoma’s Dimitrios Papavassiliou and the University of Colorado Boulder’s Joel Kaar.
Penn Dental Medicine and Penn Engineering, which teamed earlier this year to launch the Center for Innovation and Precision Dentistry (CiPD), recently awarded the Center’s first IDEA (Innovation in Dental Medicine and Engineering to Advance Oral Health) Prize. Dr. Henry Daniell, W.B. Miller Professor and Vice Chair in the Department of Basic & Translational Sciences at Penn Dental Medicine, and his collaborator, Dr. Daeyeon Lee, Professor of Chemical and Biomolecular Engineering at Penn Engineering, are the inaugural recipients, awarded the Prize for a project titled “Engineered Chewing Gum for Debulking Biofilm and Oral SARS-CoV-2.”
“The IDEA Prize was created to support Penn Dental and Penn Engineering collaboration, and this project exemplifies the transformative potential of this interface to develop new solutions to treat oral diseases,” says Dr. Michel Koo, Professor in the Department of Orthodontics and Divisions of Pediatric Dentistry and Community Oral Health at Penn Dental Medicine and Co-Director of the CiPD.
“The prize is an exciting opportunity to unite Drs. Lee and Daniell and their vision to bring together state-of-the-art functional materials and drug-delivery platforms,” adds Dr. Kathleen Stebe, CiPD Co-Director and Goodwin Professor of Engineering and Applied Science at Penn Engineering.
Open to faculty from Penn Dental Medicine and Penn Engineering, the IDEA Prize, to be awarded annually, supports collaborative teams investigating novel ideas using engineering approaches to kickstart competitive proposals for federal funding and/or private sector/industry for commercialization. Awardees are selected based on originality and novelty; the impact of the proposed innovation of oral/craniofacial health; and the team composition with complementary expertise. Indeed, the project of Drs. Daniell and Lee reflects all three.
The collaborative proposal combines Dr. Daniell’s novel plant-based drug development/delivery platform with Dr. Lee’s novel polymeric structures to create an affordable, long-lasting way to reduce dental biofilms (plaque) and oral SARS-CoV-2 transmission using a uniquely consumer-friendly delivery system — chewing gum.
“Oral diseases afflict 3.5 billion people worldwide, and many of these conditions are caused by microbes that accumulate on teeth, forming difficult to treat biofilms,” says Dr. Daniell. “In addition, saliva is a source of pathogenic microbes and aerosolized particles transmit disease, including COVID-19, so there is an urgent need to develop new methods to debulk pathogens in the saliva and decrease their aerosol transmission.”
DNA Microscopy Gives a Better Look at Cell and Tissue Organization
A new technique that researchers from the Broad Institute of MIT and Harvard University are calling DNA microscopy could help map cells for better understanding of genetic and molecular complexities. Joshua Weinstein, Ph.D., a postdoctoral associate at the Broad Institute, who is also an alumnus of Penn’s Physics and Biophysics department and former student in Penn Bioengineering Professor Ravi Radhakrishnan’s lab, is the first author of this paper on optics-free imaging published in Cell.
The primary goal of the study was to find a way of improving analysis of the spatial organization of cells and tissues in terms of their molecules like DNA and RNA. The DNA microscopy method that Weinstein and his team designed involves first tagging DNA, and allowing the DNA to replicate with those tags, which eventually creates a cloud of sorts that diffuses throughout the cell. The DNA tags subsequent interactions with molecules throughout the cell allowed Weinstein and his team to calculate the locations of those molecules within the cell using basic lab equipment. While the researchers on this project focused their application of DNA microscopy on tracking human cancer cells through RNA tags, this new method opens the door to future study of any condition in which the organization of cells is important.
If you’ve ever pressed a picture-hanging strip onto the wall only to realize it’s slightly off-center, you know the disappointment behind adhesion as we typically experience it: it may be strong, but it’s mostly irreversible. While you can un-stick the used strip from the wall, you can’t turn its stickiness back on to adjust its placement; you have to start over with a new strip or tolerate your mistake. Beyond its relevance to interior decorating, durable, reversible adhesion could allow for reusable envelopes, gravity-defying boots, and more heavy-duty industrial applications like car assembly.
Such adhesion has eluded scientists for years but is naturally found in snail slime. A snail’s epiphragm — a slimy layer of moisture that can harden to protect its body from dryness — allows the snail to cement itself in place for long periods of time, making it the ultimate model in adhesion that can be switched on and off as needed. In a new study, Penn Engineers demonstrate a strong, reversible adhesive that uses the same mechanisms that snails do.
Low-Dose Radiation CT Scans Could Be Improved by Machine Learning
Machine learning is a type of artificial intelligence growing more and more popular for applications in bioengineering and therapeutics. Based on learning from patterns in a way similar to the way we do as humans, machine learning is the study of statistical models that can perform specific tasks without explicit instructions. Now, researchers at Rensselaer Polytechnic Institute (RPI) want to use these kinds of models in computerized tomography (CT) scanning by lowering radiation dosage and improving imaging techniques.
A recent paper published in Nature Machine Intelligence details the use of modularized neural networks in low-dose CT scans by RPI bioengineering faculty member Ge Wang, Ph.D., and his lab. Since decreasing the amount of radiation used in a scan will also decrease the quality of the final image, Wang and his team focused on a more optimized approach of image reconstruction with machine learning, so that as little data as possible would be altered or lost in the reconstruction. When tested on CT scans from Massachusetts General Hospital and compared to current image reconstruction methods for the scans, Wang and his team’s method performed just as well if not better than scans performed without the use of machine learning, giving promise to future improvements in low-dose CT scans.
A Mind-Controlled Robotic Arm That Requires No Implants
A new mind-controlled robotic arm designed by researchers at Carnegie Mellon University is the first successful noninvasive brain-computer interface (BCI) of its kind. While BCIs have been around for a while now, this new design from the lab of Bin He, Ph.D., a Trustee Professor and the Department Head of Biomedical Engineering at CMU, hopes to eliminate the brain implant that most interfaces currently use. The key to doing this isn’t in trying to replace the implants with noninvasive sensors, but in improving noisy EEG signals through machine learning, neural decoding, and neural imaging. Paired with increased user engagement and training for the new device, He and his team demonstrated that their design enhanced continuous tracking of a target on a computer screen by 500% when compared to typical noninvasive BCIs. He and his team hope that their innovation will help make BCIs more accessible to the patients that need them by reducing the cost and risk of a surgical implant while also improving interface performance.
KIChE is an organization that aims “to promote constructive and mutually beneficial interactions among Korean Chemical Engineers in the U.S. and facilitate international collaboration between engineers in U.S. and Korea.”
We would also like to congratulate Natalia Trayanova, Ph.D., of the Department of Biomedical Engineering at Johns Hopkins University on being inducted into the Women in Tech International (WITI) Hall of Fame. Beginning in 1996, the Hall of Fame recognizes significant contributions to science and technology from women. Trayanova’s research specializes in computational cardiology with a focus on virtual heart models for the study of individualized heart irregularities in patients. Her research helps to improve treatment plans for patients with cardiac problems by creating virtual simulations that help reduce uncertainty in either diagnosis or courses of therapy.
Finally, we would like to congratulate Andre Churchwell, M.D., on being named Vanderbilt University’s Chief Diversity Officer and Interim Vice Chancellor for Equity, Diversity, and Inclusion. Churchwell is also a professor of medicine, biomedical engineering, and radiology and radiological sciences at Vanderbilt, with a long career focused in cardiology.
A new technique that researchers from the Broad Institute of MIT and Harvard University are calling DNA microscopy could help map cells for better understanding of genetic and molecular complexities. 
