Genetically Engineering Transplantable Organs to Signal Early Signs of Rejection

BME professor's collaborative study demonstrates a potentially transformative method to diagnose and treat organ rejection

For transplantation medicine practitioners, a persistent challenge is identifying early signs of organ rejection in the more than 40,000 transplants performed each year in the U.S. The results of a new study published in the January 2026 issue of Molecular Therapy explores a potentially game-changing direction for improving long-term transplant survival and patient outcomes. 

Biju Parekkadan, a professor in the School of Engineering's Department of Biomedical Engineering (BME), was a Co-PO on the study's international team of researchers from Massachusetts General Hospital, Harvard University; Shriner's Children's Hospital; and University Medical Center, Utrecht, the Netherlands. 

The team's innovative project makes the case for the potential of genetically engineered transplant organs to detect transplanted organ rejection earlier and more accurately — and ultimately improve patient survival. 

"We used a lentivirus to deliver a new gene to organs for long-term stable expression, that is performed with the support of machine perfusion to preserve and keep several major organs like kidneys and hearts viable before transplanting," Parekkadan explains. 

So far, he adds, "the combination of machine perfusion's facilitating genetic engineering has been performed only on rodents with promising results."

The study's researchers reported organ rejection using the team's genetic sensor — a secreted sensitive blood-based biomarker — six days before clinical symptoms were apparent, thus providing a longer window for clinical intervention and treatment. 

Ongoing — and Funded — Research

Parekkadan is a Primary Investigator (PI) on two multi-year grants. "The National Institutes of Health (NIH) and Department of Defense (DoD) have recently funded this work to help accelerate further development." 

The NIH grant supports work to scale up the organ engineering approach to large animal vascular composite allografts (VCA) guided by pharmacological modeling. The DoD award funds the development of a next-generation gene therapy that encodes both an optimized diagnostic sequence and a new immunotherapy sequence to simultaneously detect and treat rejection in a VCA small animal model system for initial studies.

Better Patient Management

While Parekkadan notes that human trials are likely to be five years away, the transformative potential of identifying early transplant rejection is tremendous. He reports that he is most excited by "the opportunity to use a blood biomarker for better patient management as well as the opportunity to add immunotherapies to the genetic system to try to slow rejection."

With the eventual advances in early reporting of organ rejection, he expects that "physicians may respond by conducting further diagnostic testing and/or using immunosuppressants in a more active way. Furthermore, by seeing the blood marker go down with medical care, they could have additional assurance that their medical intervention was successful."