15 projects named to this year’s class of technologies with high potential for positive impact
Every year the Wyss Institute names a class of Validation Projects whose teams receive dedicated funding, business development support, and other resources to advance their promising technologies towards commercialization. They also collaborate with key opinion leaders, investors, and potential customers to de-risk their innovations and speed their progress to the market.
This year, we’re thrilled to be supporting 15 projects that are working to solve critical problems across fields from skin diseases to diagnostics to PFAS contamination. Seven projects are co-led by Wyss faculty members collaborating across disciplines (and sometimes continents), and three are focused on applying biologically inspired engineering to sustainability.
Renewed projects
Brain-targeted nanoparticles: Better treatment of brain diseases
Team Leads: Maria Poley, Jiapeng Wang
Faculty: Natalie Artzi, Don Ingber
Contact: Sam Inverso
Brain diseases like Parkinson’s, Alzheimer’s, cancers, and rare genetic diseases are difficult to treat because most drugs cannot efficiently cross the blood-brain barrier (BBB), which naturally shields the brain from most substances in the blood. This project team is developing a novel drug delivery platform that attaches engineered drug-carrying nanostructures to brain shuttle molecules. These brain-targeted nanoparticles are designed to more effectively transport a wide variety of drugs across the BBB.
COPDx: Diagnostics to rapidly triage chronic obstructive pulmonary disease
Team Lead: Tiffany Lin, Rushdy Ahmad, Mike Super
Faculty: Don Ingber, David Walt
Contact: Gretchen Fougere
Chronic obstructive pulmonary disease (COPD) affects 15.9 million U.S. adults, costing $49 billion annually. When COPD flares up in acute exacerbations (AE), doctors need to evaluate patients in person by cobbling together symptoms without an accurate diagnostic tool. COPD patients also often lack mobility and access to diagnostic labs. Together with Brigham and Women’s Hospital, we’re developing diagnostic tests for new AE-correlated biomarkers to identify patients who are at high risk of AE, and determine its causes. Results can be sent to a smartphone app and allow doctors to remotely diagnose or triage patients, saving lives and reducing healthcare costs.
DNA nanoswitch calipers for single-molecule proteomics
Team Leads: Andrew Ward, Prakash Shrestha
Faculty: William Shih, Wesley Wong
Contact: Ally Chang
Proteins are well known as essential orchestrators of life, but what is less well-understood is their post-translational modifications (PTMs). Certain protein PTMs have been linked to diabetes, cancer, and neurodegenerative disease, but studying them is a challenge. DNA nanoswitch calipers (DNCs) offer a transformative approach to proteomics, marrying DNA nanotechnology with single-molecule manipulation techniques. This next-generation platform enables high-throughput analysis of protein PTMs, which could unlock profound advances in our understanding of health and disease, as well as biomedicine.
Lactation Biologics: Increasing milk production for healthier babies
Team Lead: Kasia Kready
Faculty: Pamela Silver
Contact: Gretchen Fougere
Babies are born to breastfeed, but 50% of lactating people struggle to make enough milk for them. Despite this problem, there are no FDA-approved drugs to increase milk supply. While baby formula is promoted as an alternative, the medical community unanimously agrees that breastmilk provides ideal nutrition and should be newborns’ primary food source. Baby formula is also subject to supply chain disruptions and recalls, and requires clean water, which is unavailable during climate disasters. Lactation Biologics has created an engineered form of the protein prolactin (the protein that naturally induces milk production) that boosts lactation for a sustained period of time in mice, and is developing a data package for commercialization.
ProTx: Enhanced thymic regeneration and reconstitution
Team Leads: Mary Catherine Skolfield, Kwasi Adu-Berchie
Faculty: Dave Mooney
Contact: Paul Resnick
The thymus is essential for T cell development, which plays a vital role in human immune responses, but its function declines with age and disease. Certain cytokines have been identified as important mediators of thymic repair, but they can trigger negative side effects when administered intravenously. To overcome this issue, we are generating T cell precursors known as “progenitor T cells” and equipping them with beneficial cytokines that promote thymic regeneration. The progenitor T cells travel directly to the thymus when injected and deliver these cytokines locally with minimal side effects.
New projects
A-Seq: Antibody discovery by sequencing
Team Leads: Michel Nofal, Namita Sarraf, Kuanwei Sheng
Faculty: Peng Yin
Contact: Sam Inverso
Biologics have revolutionized modern medicine – it is predicted that five of the 10 most profitable drugs in 2024 will be antibodies. A-Seq is a streamlined drug discovery pipeline that identifies antibodies against therapeutic targets using novel sequencing technology. Critically, this method leapfrogs the most labor-intensive and failure-prone steps of traditional antibody discovery pipelines. Eliminating these hurdles will enable A-Seq to do antibody discovery at scale, generating more candidate therapeutics in less time.
CyanoPro: Fast-growing cyanobacteria for sustainable protein secretion
Team Leads: Elizabeth Hann, Tzu-Chieh Tang
Faculty: George Church
Contact: Alex Li
Recombinant proteins are an increasingly common source of enzymes and drugs, but their production is very energy- and resource-intensive, causing large amounts of carbon emissions. CyanoPro aims to develop a sustainable biomanufacturing platform using fast-growing, photosynthetic cyanobacteria that can secrete various functional proteins including enzymes and therapeutics, minimizing environmental impact while lowering the cost of downstream processing.
ENTER: Protein nanoparticles for therapeutic macromolecule delivery
Team Leads: Sayo Eweje, Jiaxuan Chen
Faculty: Don Ingber, Elliot Chaikof
Contact: Bill Bedell
Gene replacement and gene editing have the potential to treat many genetic disorders, but their use is limited by a lack of efficient delivery methods. Elastin-based Nanoparticles for Therapeutic delivERy (ENTER) is a non-viral, self-assembling recombinant protein nanoparticle system that can efficiently deliver various nucleic acid and protein cargoes to a number of organs and cell types. This Validation Project is using ENTER to improve treatment of cystic fibrosis, a life-threatening disease that affects over 100,000 people globally and for which there is no treatment that addresses the underlying genetic cause of the disease.
GeneSkin: A novel mRNA therapy for skin rejuvenation and scar treatment
Team Lead: Li Li
Faculty: George Church
Contact: Bill Bedell
Despite decades of research, the molecular mechanisms that regulate skin rejuvenation are largely unknown, which has limited treatments for many skin diseases to symptom management. The GeneSkin team has discovered novel gene targets that regulate scar formation and fibrosis, and aims to validate new disease-modifying approaches based on these targets in in vitro and in vivo models.
Microfluidic monitoring device for rapid prediction of blood clots in mesothelioma patients
Team Leads: Abidemi Junaid, Adama Sesay
Faculty: Don Ingber
Contact: Gretchen Fougere
Malignant pleural mesothelioma (MPM) is an aggressive lung cancer that often requires surgery. The top cause of death in MPM patients who undergo surgery is deep vein thrombosis (DVT), in which a blood clot causes a pulmonary embolism in the lung. There is currently no way to identify patients who are at risk of DVT. This project team has created a microfluidic chip device that can monitor the blood for evidence of clotting. They plan to develop their proof-of-concept into a robust, user-friendly diagnostic test to predict MPM patients who are at risk of developing blood clots to enable better disease monitoring and save lives.
Nixe: Environmentally responsible water-repellent textile finishes
Team Lead: Caroline Dignes
Faculty: Joanna Aizenberg
Contact: Alex Li
Long chain per- and polyfluorinated chemical compounds, commonly called PFAs, have long offered superior breathable and flexible water repellent finishes on textiles, making them difficult to replace in high-performance products. Now notoriously deemed “forever chemicals” for their environmental persistence and ability to accumulate in the blood of people and animals, they can cause health problems including cancer and reproductive harm. Inspired by the microscopically bumpy surface of water repellent lotus leaves, Nixe is creating a robust, flexible, and breathable interface between fabric and water to offer a PFA-free, water-repellent textile solution.
PFASense: Biosensors for PFAS monitoring
Team Lead: Simon D’Oelsnitz
Faculty: Pam Silver, Mike Springer
Contacts: Alex Li, Sam Inverso
Because of their long-term persistence in the environment, PFAs are being discovered contaminating more and more places. PFASense aims to develop protein-based biosensors for PFAs monitoring. The biosensor scaffold will be engineered to produce a detectable signal in bacteria, then screened for those that can indicate the presence of PFAs. Established directed evolution methods will then be used to refine the lead biosensor candidates to achieve target specificity and sensitivity.
RAPID-Vasc: Rapid assembly and perfusion for implant and device vascularization
Team Leads: Chris Chen, Subramanian Sundaram
Faculty: Chris Chen, Don Ingber
Contact: Gretchen Fougere
Despite three decades of significant progress in tissue engineering, a persistent challenge remains: generating networks of blood vessels to support thick, engineered tissues. This project is developing a new approach to rapidly assemble networks of hollow channels within cell-laden hydrogels, generating high-cell-density engineered vasculature for both in vitro and in vivo applications.
SCHISM: Deep library screening to reprogram proteases
Team Lead: Stefan Zukin
Faculty: George Church
Contact: Bill Bedell
Multiple FDA-approved therapeutics are proteases – enzymes that cut target proteins at specific amino acid sequences to either activate or inactivate them – but, to date, the clinical use of proteases has been limited to naturally-discovered proteases. This project aims to unlock a new class of drugs by using large mutant protease libraries coupled with machine learning to model the protease fitness landscape and enable the design of custom proteases that cut at desired sequences.
TIB: Tolerance-inducing biomaterials
Team Lead: Kwasi Adu-Berchie
Faculty: Dave Mooney, Georg Duda
Contact: Ally Chang
T regulatory cell (Treg) therapies hold immense promise for treating a wide variety of diseases, but targeting them to specific tissues in the body and maintaining their efficacy long-term are persistent challenges. Tolerance-Inducing Biomaterials (TIB) can be used to deliver Tregs to specific tissues, and create a niche to maintain their function over extended time periods. These materials can also be used to transform T effector cells (Teff) into Tregs at disease sites, simultaneously removing tissue-destructive cells while delivering pro-regenerative cells.