CAMBRIDGE, MA—Scientists have long known that our environment can affect the way our genes work, a process called gene expression. Now they want to find out how to temporarily and reversibly tune gene expression to bolster the body’s defenses against—or to directly neutralize—a given threat.
A catalyst for this work is DARPA’s new program called PReemptive Expression of Protective Alleles and Response Elements (PREPARE). The goal of PREPARE is to deliver novel and effective defenses against public health and national security threats.
With funding from PREPARE, a team from Draper, the University of Massachusetts Medical School (UMMS) and Massachusetts General Hospital (MGH) is aiming to develop new approaches for identifying innate host genetic defenses against influenza and new medical countermeasures (MCMs) that can quickly activate and modulate individual genes to boost protection—all with reversible processes that do not alter the underlying genetic code.
The team’s target environmental stressor is influenza, which represents a challenge because seasonal flu vaccines are required to hit a perpetually moving target, and therefore circulating flu strains are often mismatched to vaccine strains. Data show that the 2018-2019 flu vaccine was only 29 percent effective.
Military service members, first responders and civilian populations are among those who could benefit from PREPARE, said the agency in announcing the program. Renee Wegrzyn, the DARPA PREPARE program manager, said neutralizing more viral strains and giving a temporary boost to a person’s protection genes “could change how we think about anti-virals.”
The team of engineers and clinical researchers, led by the UMass Medical School, along with Draper and MGH, is applying new insights from the fields of genome editing and in vivo delivery to develop safe, programmable and transient treatments for influenza.
To evaluate the new treatments, Draper will use its PREDICT-96, a human organ system platform that can be easily integrated into existing lab automation and screening tools. The system functions by integrating 96 independent models of a human organ on a single plate the size of an index card. The team will assess the efficacy and safety of emerging treatments for diseases by replicating human responses in a laboratory model system—in this case, influenza infections using human cells cultured in microscale models that accurately represent the disease process in the human airway.
“Using patient-derived cells in tissue models to test vaccines and other therapies is relatively new to drug development, but the technique shows promise for being more accurate than animal tests,” said Draper’s Jeff Borenstein, Ph.D., co-Principal Investigator (PI) on the UMMS team. “A microenvironment that can sustain human tissue organ models for several weeks of automated testing will be important for developing new tools for fighting public health threats like the seasonal flu.”
Borenstein added that this is the first instance of creating a dynamic air-liquid interface model using patient-derived cells for influenza testing.
The project is an important one for Draper and it is part of a larger and growing biosecurity and synthetic biology portfolio that includes new technology for DNA synthesis and molecular information storage and tools for bacterial detection and antibiotic susceptibility testing.