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The Wyss Institute’s 2023-2024 Validation Projects

13 projects selected to receive Validation Project support to advance commercialization and impact

Each year we name a class of Validation Projects whose teams receive dedicated funding, business development support, and additional resources to advance their technologies towards commercialization.

Over the course of the year, project teams pursue initial use-cases for their technologies that have the potential for significant positive impact. They also collaborate with key opinion leaders, investors, and potential customers to de-risk their innovations and speed their progress to the market.

The Wyss Institute’s 2023-2024 Validation Projects
DNA Nanoswitch Calipers (DNCs) combine DNA nanotechnology with single-molecule manipulation to measure atomic-level distances, allowing for protein identification and 3D mapping of molecular complexes at the single-molecule level. Credit: Wyss Institute at Harvard University

DNA Nanoswitches: Single-molecule proteomics

Team Lead: Andrew Ward
Faculty: William Shih, Wesley Wong
Contact: Ally Chang

Proteins, essential orchestrators of life and disease, must be understood in detail to enable their use in basic research and practical applications in diagnostics and therapeutics. DNA Nanoswitch Calipers (DNCs) offer a transformative approach to proteomics, marrying DNA nanotechnology with single-molecule manipulation to measure atomic-level distances. This allows for protein identification and 3D mapping of molecular complexes at the single-molecule level. This next-generation platform promises profound advances in molecular understanding, biomedicine, and drug innovation. Part of Northpond Labs alliance.

The Wyss Institute’s 2023-2024 Validation Projects
50% of moms struggle to make enough milk for their babies. We’re developing protein therapeutics to help them increase lactation. Credit: Envato Elements/crystalsing

Lactation Biologics: Enhancing lactation to improve infant and maternal health

Team Leads: Kasia Kready, Jeffrey Way
Faculty: Pamela Silver
Contact: Gretchen Fougere

Infants are born to breastfeed, but 50% of moms struggle to make enough milk for them. In addition to providing the best nutrition possible, breast milk is also a crucial source of food for babies during power outages, supply chain disruptions, and in places without access to clean water. To help mothers and their infants, we’re developing protein therapeutics to increase lactation. Protecting breastfeeding is imperative for advancing women’s health equity and creating resilient infant feeding systems in an age of increasing natural disasters and climate crises.

Duplex RNA Tx: A new approach to fighting cancer

Team Leads: Sylvie Bernier, Ken Carlson
Faculty: Natalie Artzi, Don Ingber, William Shih
Contact: Ally Chang, Alex Li

Cancer is one of the leading causes of death worldwide. By 2040, new cancer cases are expected to rise to 29.5 million and cancer-related deaths could reach 16.4 million. We identified a new class of immunostimulatory short duplex RNAs that induce production of interferons that can inhibit the growth and spread of cancer cells, which has significant potential as anti-cancer drugs or could be used in combination with current treatment options, such as immune checkpoint inhibitors. These powerful stimulators of the immune system could also be used to treat respiratory viruses, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A.

The Wyss Institute’s 2023-2024 Validation Projects
AminoX team members Michaël Moret, Helena de Puig, and Erkin Kuru (from left to right) at the Wyss Institute. Credit: Wyss Institute at Harvard University

AminoX: Engineering immunotherapies for conditional activity in solid tumors

Team Leads: Helena de Puig, Erkin Kuru, Michaël Moret
Faculty: George Church, Jim Collins, Don Ingber
Contact: Bill Bedell

Cancer treatments like immune checkpoint inhibitor drugs can significantly prolong patients’ lives but can have severe side effects, forcing up to 36% of patients to discontinue therapy. To create safer immune checkpoint inhibitor protein drugs, we are incorporating non-standard amino acids (nsAAs) that enable them to become active only in tumors. Our AminoX platform bypasses traditional challenges of protein engineering and significantly expands the range of available nsAA structures with unique functionalities.

ViroScreen: Screening the virome for in vivo RNA delivery

Team Leads: Siddharth Iyer, Dima Ter-Ovanesyan, Henry Zhou
Faculty: George Church
Contact: Bill Bedell

Gene editing could be a permanent cure for many diseases but is limited by our inability to deliver large mRNAs encoding gene editors to organs besides the liver – adeno-associated viruses (AAVs) have small cargo capacity and lipid nanoparticles (LNPs) cannot escape the liver. We are exploring diverse viruses across the virome to develop novel virus-like particles for delivery to a variety of cell types. Our initial focus is delivering RNA to T cells for in-vivo CAR-T against multiple myeloma.

T Cell Immunity: Enhanced thymic regeneration and reconstitution

Team Lead: Hamza Ijaz
Faculty: Dave Mooney
Contact: Paul Resnick

The thymus is essential for T cell development, which plays an important role in the immune response to cancer, but its function can deteriorate due to age and various diseases. Cytokines could help repair the thymus but can also trigger unintended systemic effects. To overcome this issue, we’re generating early-stage T cells, known as progenitor T cells, and are equipping them with beneficial cytokines that promote thymus healing by migrating to the thymus and delivering cytokines with minimal systemic issues.

The Wyss Institute’s 2023-2024 Validation Projects
Girija Goyal, Ph.D. is leading a team to identify new immunotherapy treatments for pancreatic cancer. Credit: Wyss Institute at Harvard University

TLO Tx: Fighting pancreatic cancer

Team Lead: Girija Goyal
Faculty: Don Ingber
Contact: Gretchen Fougere

Patients burdened by tumors sometimes develop lymph-node-like clumps of immune cells called Tertiary Lymphoid Organs (TLOs) close to the tumor that seem to improve their response to therapy. We are developing models of pancreatic cancer tumors with TLOs to identify molecules that affect TLO function, and novel immunotherapy targets that leverage TLOs’ tumor-suppressive abilities.

AquaPulse: Portable off-the-grid water purification

Team Leads: Adama Sesay, Emily Stoler
Faculty: Don Ingber
Contact: Alex Li

Around 2.6 billion people globally do not have access to clean water. Waterborne bacteria, parasites, and other pathogens lead to illness, with an estimated half a million people dying each year from diarrhea as a result of unsafe drinking water. We’re developing a portable, off-the-grid water purification and sterilization system that kills bacteria, parasites, and viruses, making contaminated water safer to drink without the need for expensive filters or bulky machinery.

directEsense: Diagnostics for animal health

Team Lead: Nandhinee Radha Shanmugam
Faculty: Don Ingber
Contact: Alex Li

Currently, most veterinary diagnostics are conducted in centralized labs, which can be costly, slow, and difficult to access. Leveraging a validated Wyss-invented highly sensitive and specific sensor technology, we’re developing directEsense, a handheld, label-free diagnostic device that could enable rapid, accurate, and cost-effective testing for a variety of diseases and biomarkers directly from fluid samples at veterinary offices, farms, stables, or at home.

Senior patient in breathing mask lies in the ward during treatment for Covid-19. High quality photo
COPDx is a point-of-care test that can differentiate between viral and bacterial causes of acute exacerbations of COPD. Credit: Envato Elements/astakhovyaroslav

COPDx: Triaging COPD acute exacerbations

Team Leads: Rushdy Ahmad, Tiffany Lin, 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 clinical collaborators at Brigham and Women’s Hospital, we’re developing a point-of-care test with new AE-correlated biomarkers to differentiate between viral and bacterial causes. Results can be sent to a smartphone app and allow doctors to remotely diagnose or triage patients, saving lives and healthcare costs.

Brain-Targeted Nanoparticles: Systemic treatment of brain diseases

Team Leads: Maria Poley, Jiuhai Wang, James Gorman
Faculty: Natalie Artzi, Don Ingber
Contact: Sam Inverso
Additional Team Members: Liqun Wang and Yifei Lu

Brain diseases, such as Parkinson’s, Alzheimer’s, cancers, and rare genetic diseases, are difficult to treat because most drugs are not able to cross the blood-brain barrier (BBB), which naturally shields the brain from unwanted molecules and toxins. We’re developing a novel brain-targeted drug delivery platform by packaging engineered antibody shuttles into specifically engineered nanostructures to improve the efficiency of transport across the BBB.

The Wyss Institute’s 2023-2024 Validation Projects
HarborSite researchers Tina Lebar (middle) and Erik Aznauryan (right) are developing a next-generation gene therapy platform and receive support from Wyss business development manager Bill Bedell (left). Credit: Wyss Institute at Harvard University

HarborSite: Precise and efficient genome editing for safe and durable gene therapies

Team Leads: Erik Aznauryan, Tina Lebar
Faculty: George Church
Contact: Bill Bedell

Many human diseases can only be addressed by replacing defective genes with their functional copies, but achieving safe, long-term expression of these therapeutic genes is challenging. We are developing a novel gene writing platform that uses highly efficient site-specific recombinases to enable targeted insertion of entire genes into genomic “safe harbors” for their durable expression, resulting in curative treatments.

Ichor: Treating age-related diseases with cell rejuvenation

Team Lead: Alex Plesa
Faculty: George Church, Don Ingber
Contact: Bill Bedell

Age is a major risk factor for numerous chronic conditions, many of which arise from age-related dysfunctions in hematopoietic stem cells (HSC). This functional decline is evident in HSC transplantation (HSCT), where HSCs from older donors result in reduced survival rates of recipients, compared to HSCs from younger donors. We’re developing “transcriptomic reprogramming” techniques for HSC rejuvenation to improve outcomes for HSCT patients. This research also has the potential to provide insights that could help improve overall human health and extend lifespan for the broader population.

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