Boston Children’s Hospital’s Technology Development Fund (TDF) to designed to transform early-stage academic technologies into validated, high-impact opportunities for licensees and investors. Since 2009, the hospital has committed $7.6 million to support 76 promising technologies, from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. The TDF also assists with strategic planning, intellectual property protection, regulatory requirements and business models. Investigators can access mentors, product development experts and technical support through a network of contract research organizations, development partners and industry advisors.
Eight startup companies have spun out since TDF’s creation, receiving $82.4 million in seed funding. They include Affinivax, a vaccine company started with $4 million from the Gates Foundation, and Epidemico, a population health-tracking company acquired by Booz Allen Hamilton. TDF has also launched more than 20 partnerships, received $26 million in follow-on government and foundation funding and generated $4.45 million in licensing revenue.
Here are the projects TDF awarded in 2017, with grants totaling $650,000:
Delivering oxygen into tumors to enhance radiotherapy
A lack of oxygen within solid tumors is well known to diminish the efficacy of radiotherapy. Oxygen, a natural and potent “radio-sensitizer,” increases the effectiveness of radiation therapy by forming DNA-damaging free radicals. Brian Polizzotti, PhD (Department of Cardiology) and colleagues have developed injectable hollow microparticles, which contain and release large quantities of oxygen gas. The team is using TDF funds to investigate whether these oxygen-loaded microbubbles could increase efficacy of radiotherapy in a in a mouse model of carcinoma.
A filtration technology to treat systemic inflammatory response syndrome
Compounding the damage of sepsis — bloodstream infection — is the inflammatory cascade it triggers. Brian McAlvin, MD, Daniel Kohane, MD, PhD (Critical Care Medicine) and colleagues have developed silicone-based blood-filtering devices that selectively remove harmful proteins from patients’ blood. The device surfaces are modified with antibodies (Antibody-Modified Conduits, or AMCs) that recognize circulating proteins. To date, the team has targeted the systemic inflammatory response syndrome (SIRS) with AMCs built to specifically eliminate cytokines, a class of proteins that stimulate inflammation. McAlvin describes the technology in this five-minute talk:
With support from a 2014 TDF award, the investigators showed that their device can accomplish selective cytokine filtration in a rat model of SIRS. TDF 2017 funds are being used to expand the work to a large animal model to demonstrate that the technology is scalable.
Automated tests to assess rodents’ behaviors — from their footwork
Rodent behavioral assays are indispensable in studying neurological dysfunction, but making them clinically relevant has been difficult, particularly in the prediction of drug efficacy and side effects. David Roberson, PhD, MBA and Clifford Woolf, MB, BCh, PhD (F.M. Kirby Neurobiology Center) have invented a novel technology that can infer neurological function and disease states by analyzing the footprints and somatic behaviors of freely behaving rodents in the dark — the ideal state to study nocturnal animals. Roberson describes the technology in this five minute pitch:
With support from a TDF 2015 award, the team developed a user-friendly software package that permits automated detection and scoring of spontaneous rodent behaviors. TDF 2017 funds are being used to apply machine learning approaches to robustly identify behavioral patterns indicative of specific neurological activity.
A novel whole-cell vaccine for diarrheal disease
Diarrhea caused by intestinal pathogens is the primary cause of illness and the second most common cause of death among children in resource-poor countries. Recently, enterotoxigenic Escherichia coli and Shigella have been identified as the two most common causes of bacterial diarrhea in children under 5, yet no vaccines targeting these pathogens are available. But short of improved sanitation, vaccination is the best means of disease prevention.
With support from a TDF 2013 award, Paula Watnick, MD, PhD and Julie Liao, PhD (Division of Infectious Diseases) developed and tested a novel antigen presentation platform derived from live, attenuated V. cholerae. Through genetic engineering, V. cholerae were made to overproduce a protein that accumulates in bacterial biofilms and elicits an immune response. The team has also tested this platform with enterotoxigenic E. coli antigens and demonstrated a robust immune response. TDF 2017 funds are extending this approach to Shigella.
A microphysiologic tissue construct for age-specific vaccine development
Infections claim millions of lives every year, especially among newborns and infants less than 6 months of age, whose distinct immune systems render them particularly susceptible. Vaccines are a highly cost-effective measure to reduce global morbidity and mortality, but development of vaccines is empiric, costly and slow, and most vaccines do not work in newborns. To accelerate and de-risk vaccine development, Ofer Levy, MD, PhD and Guzman Sanchez-Schmitz, MSc, PhD (Precision Vaccines Program/Division of Infectious Diseases) created three-dimensional tissue constructs containing immune cells that accurately model age-specific human vaccine responses. TDF funds are helping the team further validate the tissue construct technology in vivo with the pneumococcal conjugate vaccine.
Shape-shifting DNA nanoswitches as low-cost biomarkers
WATCH: DNA nanoswitches change shape in the presence of biomarkers, revealed during a standard gel electrophoresis. Credit: Wyss Institute at Harvard University
Wesley Wong, PhD (Program in Cellular and Molecular Medicine) and his team have developed a technology for ultra-sensitive detection of a wide array of chemicals. The system uses DNA-based molecular probes that change shape when they bind to biomarkers of interest, thereby functioning as “nanoswitches.” The method can identify biomarkers rapidly, at low cost, and can enable single-molecule mechanical detection.
To date, the team has demonstrated high-sensitivity detection of prostate-specific antigen in complex biological fluids, and high-specificity detection of different dengue virus nonstructural proteins. The team is using TDF funds to optimize nanoswitch-based detection in biological fluids and validate the utility of nanoswitch detection for cancer and/or infectious diseases.
Are you a Boston Children’s scientist or clinician? TDF 2018 funding applications open January 16. Check our website for information.
If you’re from industry and wish to inquire about a technology, contact the Technology and Innovation Development Office.