Penn Engineers Will Use NSF Grant to Develop ‘DReAM’ for On-demand, On-site mRNA Manufacturing

by Melissa Pappas

Daeyeon Lee, Kathleen Stebe and Michael Mitchell

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.

Read the full story in Penn Engineering Today.

Penn Dental Medicine, Penn Engineering Award First IDEA Prize to Advance Oral Health Care Innovation

Henry Daniell and Daeyeon Lee

by Beth Adams

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.”

Continue reading at Penn Dental Medicine News.

N.B. Henry Daniell and Daeyeon Lee are members of the Penn Bioengineering Graduate Group.

BE Seminar: “Synthetic Biochemistry: Engineering Molecules and Pathways for Precision Medicine” (Michael Lin)

Save the date for the first Penn Bioengineering seminar of the fall 2021 semester! This year’s seminars will be hybrids, held virtually on zoom and live on campus!

Michael Lin, Ph.D.

Speaker: Michael Lin, Ph.D.
Associate Professor
Neurobiology, Bioengineering, and by courtesy Chemical and Systems Biology
Stanford Medicine, Stanford University

Date: Thursday, September 2, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: The most effective medicines are those that target the earliest causes of disease, rather than later manifestations. Engineering of biomolecules is a promising but underexplored approach to precisely detecting or targeting disease causes. I will present our work to develop a novel approach to treating cancer by detecting the signaling abnormalities that give rise to cancer. Interestingly, this effort involves biomolecular engineering at multiple scales: proteins, pathways, and viruses. I will also discuss how our work has translated serenditously to developing treatments for SARSCoV2.

Michael Lin Bio: Michael Z. Lin received an A.B. summa cum laude in Biochemistry from Harvard, an M.D. from UCLA, and a Ph.D. from Harvard Medical School. After training in biochemistry and neurobiology as a PhD student with Michael Greenberg at Harvard Medical School, Dr. Lin performed postdoctoral research in fluorescent protein engineering with Chemistry Nobel Laureate Roger Y. Tsien at UCSD. Dr. Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, a Damon Runyon-Rachleff Innovation Award, and a NIH Pioneer Award.

Penn Engineers Create Faster and Cheaper COVID-19 Testing With Pencil Lead

by Melissa Pappas

César de la Fuente, PhD

Testing is key to understanding and controlling the spread of COVID-19, which has already taken more than four million lives around the world. However, current tests are limited by the tradeoff between accuracy and the time it takes to analyze a sample.

Another challenge of current COVID-19 tests is cost. Most tests are expensive to produce and require trained personnel to administer and analyze them. Testing in low-and middle-income communities has therefore been largely inaccessible, leaving individuals at greater risk of viral spread.

To address cost, time and accuracy, a new electrochemical test developed by Penn researchers uses electrodes made from graphite — the same material found in pencil lead. Developed by César de la Fuente, Presidential Assistant Professor in Bioengineering,  Microbiology and Psychiatry with a secondary appointment in Chemical and Biomolecular Engineering, these electrodes reduce the cost to $1.50 per test and require only 6.5 minutes to deliver 100-pecent-accurate results from saliva samples and up to 88 percent accuracy in nasal samples.

While his previous research highlights the invention of RAPID (Real-time Accurate Portable Impedimetric Detection prototype 1.0), a COVID-19 testing kit which uses screen-printed electrodes, this new research published in PNAS presents LEAD (Low-cost Electrochemical Advanced Diagnostic), using the same concept as RAPID but with less expensive materials. De la Fuente’s current test reduces costs from $4.67 per test (RAPID) to $1.50 per test (LEAD) just by changing the building material of the electrodes.

“Both RAPID and LEAD work on the same principle of electrochemistry,” says de la Fuente. “However, LEAD is easier to assemble, it can be used by anyone and the materials are cheaper and more accessible than those of RAPID. This is important because we are using an abundant material, graphite, the same graphite used in pencils, to build the electrode to make testing more accessible to lower-income communities.”

This figure, adapted from the paper, shows the functionalization steps of LEAD which prepares the electrodes to bind to the sample. The height of the peaks indicates whether the sample is negative or positive. Because the SARS-CoV-2 spike protein in a positive sample binds to the electrode, it inhibits the emitted signal and produces a smaller peak.

Read the full story in Penn Engineering Today.

Penn Bioengineering Senior Design Team Wins Hamlyn Symposium Prize

The winners of the Medical Robots for Contagious Disease Challenge Award for Best Application (L to R): Yasmina Al Ghadban, Phuong Vu, and Rob Paslaski.

Three recent Penn Bioengineering graduates took home the Best Application Award from the Medical Robotics for Contagious Disease Challenge, part of the three-month Hamlyn Symposium on Medical Robotics. Organized by the Hamlyn Centre at Imperial College, London, UK, in collaboration with the UK-RAS Network, the challenge involved “creating a 2-minute video of robotic or AI technology that could be used to tackle contagious diseases” in response to the current and potential future pandemics. Yasmina Al Ghadban, Rob Paslaski, and Phuong Vu were members of the Penn Bioengineering senior design team rUmVa who designed and built a cost-effective, autonomous robot that can quickly disinfect rooms by intelligently sanitizing high-touch surfaces and the air. The Best Application Award comes with a prize of £5,000.

The full Team rUmVa (L to R): Yasmina Al Ghadban, Rachel Madhogarhia, Phuong Vu, Jeong Inn Park, and Rob Paslaski.

Team rUmVa, which also included Bioengineering seniors Rachel Madhogarhia and Jeong Inn Park, also received a Berkman Opportunity fund grant from Penn Engineering and was one of three teams to win Penn Bioengineering’s Senior Design competition. Senior Design work is conducted every year on-site in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (which successfully reopened for in-person activities this Spring semester). Read the full list of Spring 2021 Senior Design Award Winners here.

rUmVa and the other challenge winners were honored during the Hamlyn Symposium’s virtual closing ceremony on July 29, 2021.

Read rUmVa’s abstract and final papers, along with those of all of the Penn Bioengineering Teams’, on the BE Labs Senior Design 2021 website. rUmVa’s presentation can be viewed on Youtube:

With a ‘Liquid Assembly Line,’ Penn Researchers Produce mRNA-Delivering-Nanoparticles a Hundred Times Faster than Standard Microfluidic Technologies

by Evan Lerner

Michael Mitchell, Sarah Shepherd and David Issadore pose with their new device.

The COVID vaccines currently being deployed were developed with unprecedented speed, but the mRNA technology at work in some of them is an equally impressive success story. Because any desired mRNA sequence can be synthesized in massive quantities, one of the biggest hurdles in a variety of mRNA therapies is the ability to package those sequences into the lipid nanoparticles that deliver them into cells.

Now, thanks to manufacturing technology developed by bioengineers and medical researchers at the University of Pennsylvania, a hundred-fold increase in current microfluidic production rates may soon be possible.

The researchers’ advance stems from their design of a proof-of-concept microfluidic device containing 128 mixing channels working in parallel. The channels mix a precise amount of lipid and mRNA, essentially crafting individual lipid nanoparticles on a miniaturized assembly line.

This increased speed may not be the only benefit; more precisely controlling the nanoparticles’ size could make treatments more effective. The researchers tested the lipid nanoparticles produced by their device in a mouse study, showing they could deliver therapeutic RNA sequences with four-to-five times greater activity than those made by conventional methods.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, and David Issadore, Associate Professor in Penn Engineering’s Department of Bioengineering, along with Sarah Shepherd, a doctoral student in both of their labs. Rakan El-Mayta, a research engineer in Mitchell’s lab, and Sagar Yadavali, a postdoctoral researcher in Issadore’s lab, also contributed to the study.

They collaborated with several researchers at Penn’s Perelman School of Medicine: postdoctoral researcher Mohamad-Gabriel Alameh, Lili Wang, Research Associate Professor of Medicine, James M. Wilson, Rose H. Weiss Orphan Disease Center Director’s Professor in the Department of Medicine, Claude Warzecha, a senior research investigator in Wilson’s lab, and Drew Weissman, Professor of Medicine and one of the original developers of the technology behind mRNA vaccines.

It was published in the journal Nano Letters.

“We believe that this microfluidic technology has the potential to not only play a key role in the formulation of current COVID vaccines,” says Mitchell, “but also to potentially address the immense need ahead of us as mRNA technology expands into additional classes of therapeutics.”

Read the full story in Penn Engineering Today.

“’Electronic Nose’ Accurately Sniffs Out Hard-to-Detect Cancers”

A.T. Charlie Johnson, Ph.D.

A.T. Charlie Johnson, Rebecca W. Bushnell Professor of Physics and Astronomy at the Penn School of Arts & Sciences, and member of the Penn Bioengineering Graduate Group has been working with a team of researchers on a new “electronic nose” that could help track the spread of COVID-19 based on the disease’s unique odor profile. Now, similar research shows that vapors emanating from blood samples can be tested to distinguish between benign and cancerous pancreatic and ovarian cells. Johnson presented the results at the annual American Society of Clinical Oncology meeting on June 4 (Abstract # 5544):

“It’s an early study but the results are very promising,” Johnson said. “The data shows we can identify these tumors at both advanced and the earliest stages, which is exciting. If developed appropriately for the clinical setting, this could potentially be a test that’s done on a standard blood draw that may be part of your annual physical.”

Read the full story in Penn Medicine News.

Strella Biotechnology Featured in Philly Mag

NextUp, a regular feature of Philadelphia Magazine that “highlights the local leaders, organizations and research shaping the Greater Philadelphia region’s life sciences ecosystem,” ran a profile of Philly-based agricultural startup Strella Biotechnology. Founded by Penn alumna Katherine Sizov (Bio 2019) and winner of a 2019 President’s Innovation Prize, Strella Biotech seeks to reduce food waste through innovative biosensors, and was initially developed in the George H. Stephenson Foundation Educational Laboratory, the biomakerspace and primary teaching lab of the Department of Bioengineering.

Sizov says the coronavirus pandemic has made the volatility of grocery stores’ offerings even more apparent. Last April, the Produce Marketing Association estimated that nearly $5 billion of fresh fruits and vegetables had gone to waste in the first month of the pandemic due to the complex supply chain’s inability to quickly redirect shipping and distribution. ‘In a way, I think COVID-19 has helped us realize how delicate and fragile supply chains are,’ she says. ‘We are working to create better, stronger supply chains that are economically and environmentally sustainable for everyone involved — researchers, growers, packagers, distributors, retailers, and consumers.'”

Read “NextUp: The Philly Startup Using Biosensors to Combat Food Waste and Improve Supply Chains” in Philly Mag.

Read more BE blog stories featuring Strella Biotechnology.

Guest Post: Learning About Regulatory Affairs Through a Virtual Internship

by Casey Colleran (BSE 2021, MSE 2022)

In this guest post, recent Penn Bioengineering graduate and master’s student Casey Colleran writes about her experience in virtual internship at Janssen Pharmaceuticals.

Casey Colleran

During the summer of 2020, I was privileged enough to join the Global Regulatory Affairs team at Janssen Pharmaceutical Companies of Johnson & Johnson. Despite the uncertainties brought on by COVID-19, Janssen was able to bring together a group of five interns to participate in this virtual internship. This remote opportunity provided me with a valuable understanding of Regulatory Affairs, and the pharmaceutical industry. Throughout the 11 weeks, I was able to work alongside Regulatory Scientists in several functional areas of the organization. I learned about the regulations that govern the pharmaceutical industry, and the strategy that goes into communicating with the FDA and other health authorities.

As we rotated through each of these functional areas, myself and the other interns were also able to observe how the pandemic impacted the organization. We were asked to develop our own solutions on how to address these new challenges. Through this task, I learned how to present information in a meaningful way, analyze anecdotal data, improve processes, and communicate across different networks. As a team, myself and four other interns developed probing questions to help us understand how the COVID-19 pandemic has impacted the regulatory landscape, and the different strengths and opportunities employees observed in Janssen’s response to the pandemic. As we rotated through the different functional areas of Janssen’s Global Regulatory Affairs group, we used that time to ask our questions, and make note of anecdotal data that would provide us more insight as to how to address the new challenges brought on by the pandemic, and the virtual work environment. We then created a “COVID-19 Playbook” which broke down the main themes we had heard in our responses, such as the need for a more flexible organization, more efficient and effective communication, improved connectivity in the virtual workplace, and more. We developed suggestions on programming and guidelines that would help strengthen each of these areas, and presented these suggestions to the Senior Leadership Team.

Summer 2020 Janssen interns

Leadership development opportunities were also focal to the internship. I was paired with several amazing mentors who provided me with personalized feedback on how to become a more effective leader. The culture of the organization was extremely welcoming, and I cherish the relationships that I was able to build with my colleagues, so much so that I joined Janssen as a part time contractor this past year. Through this role as a contractor, I have been able to learn more about the day-to-day activities of a Regulatory Scientist through hands-on activities. As a contractor, I have been an integral part of a new “FLEx” Program. As a part of this program, I offer support to Regulatory Scientists by taking on their more routine submissions, giving them the opportunity to work on more strategic based activities, and focus on their personal growth and learning. It has been such a wonderful experience to work closely with these Regulatory Scientists who are still early in their career, as we have been able to learn from each other as well. It has also given me a greater understanding of the regulatory landscape, and by taking part in this new program I again get to see much of my feedback be considered and implemented.

I am so grateful that I had the opportunity to work in such an amazing environment, developed so many skills, and built a network that led me to additional opportunities in Regulatory Affairs at Janssen.

Penn Health-Tech Q&A with César de la Fuente

Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)

César de la Fuente, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Microbiology, and Psychiatry, was the inaugural recipient of the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize from Penn Health-Tech in 2020 for his low-cost, rapid COVID test. Now with promising results recently published in the journal Matter (showing 90 percent accuracy in as little as four minutes), Penn Health-Tech caught up with de la Fuente to discuss his experience over the past year:

“How did [your project] evolve in the past year?

‘We started with one prototype and now have three entirely different prototypes for the test. Two use electrochemistry, and we are now working on a new technology that uses calorimetry. With calorimetry, when the cotton swabs are exposed to the virus, they change color. This means users are able to see if they’re affected by a virus through a simple color change, making it more of a visual detection method.'”

Read the full Q&A in the Penn Health-Tech blog.