A federal grant allowed researchers to develop CRISPR as a tool for gene editing, which eventually led to the ability to genetically modify pig kidneys for safe transplant into humans
Part of the Wyss Institute’s series on the positive, life-altering impact of federal research funding
By Jessica Leff
Nearly 90,000 people in the United States are waiting for a kidney transplant, and 11 people die every day while waiting for a kidney. Government funding for synthetic biology and gene therapy enabled the development of genome engineering technology that is used by a Wyss startup to engineer safe and functional pig kidneys, the first three of which have been successfully transplanted into patients, offering a new solution to this gigantic problem.
The origin of CRISPR
As early as 1987, researchers found that microbes, including bacteria and archaea, have repetitive DNA sequences, called “clustered regularly interspaced short palindromic repeats” (CRISPR), with “spacer” DNA sequences in between. These sequences exactly match viral sequences.
Eventually, scientists discovered that CRISPR functions as an antiviral defense system. When the microorganism is infected with a virus, it inserts a piece of the virus’s genome into its own to create a memory of it. CRISPR uses these viral DNA snippets to create guide RNA (gRNA), which allows the microbe to recognize the virus’s DNA in a subsequent infection and thereby destroy the invader. The protein microbes use to do this is known as “Cas,” which is short for “CRISPR-associated” nuclease.
By the early 2010s, researchers were eager to demonstrate its effectiveness in animals and humans.
Government grant for genetic engineering
In September 2010, the National Institute of Health (NIH) awarded an $18.9 million grant called Causal Transcriptional Consequence of Human Genetic Variation (CCV) to a team of researchers that included Wyss Core Faculty member George Church, Ph.D. Their goal was to develop innovative and powerful genetic engineering methods and use them to identify and understand specific genetic variations that affect the expression of genes.
Evolving the tools they created, the researchers hoped to make the ability to edit genome sequences so exact and efficient that it could become routine. Over the next five years, this ability became a reality, helping increase our understanding of how complex tissues form and function, and, more importantly, raising the possibility of gene therapies to correct or overcome disease-causing mutations in patients.
Importantly, the CCV funding was instrumental in adapting CRISPR systems for use in humans and other multicellular organisms. Church and his team succeeded in creating an RNA-guided editing tool for easy, robust, and multiplexable human genome engineering. Plus, they developed additional CRISPR systems for different purposes.
Church is also a Professor of Genetics at Harvard Medical School (HMS) and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology.
From humans to pigs to humans
From 2012-2013, Church and his team published several papers detailing their novel CRISPR systems. Upon publication, they were contacted independently by three different principal investigators with invitations to work on xenotransplantation, the transplantation of non-human cells, tissues, or organs in human recipients.
In 2015, Church and a team led by his Postdoctoral Fellow, Luhan Yang, Ph.D., used the CRISPR-Cas-9 gene editing system to inactivate all 62 copies of porcine endogenous retrovirus (PERV) found natively in the genome of pigs, which pose a risk for xenotransplantation because of their ability to infect certain human cells. The researchers published their work in Science. This opened the door for pig-to-human xenotransplantation.
When we were first awarded the CCV grant, I had no idea it would lead to xenotransplantation. But once we published that landmark paper, it started to seem quite plausible.
In 2016, eGenesis launched from the Wyss and HMS to build upon this work and develop safe and effective pig organs for transplanting into human patients.
“When we were first awarded the CCV grant, I had no idea it would lead to xenotransplantation. But once we published that landmark paper, it started to seem quite plausible,” explains Church. “Then that grant led to a third NIH Centers of Excellence in Genomic Science grant, and then eventually our TFome strategy for human stem cell-derived transplantable tissue and another startup, GC Therapeutics, which launched in 2021. All of this stemmed from that grant back in 2010, proving how many exciting, unexpected developments can start from one government grant.”
On March 16, 2024, after years of technology refinement and development, surgeons from Massachusetts General Hospital successfully transplanted the first CRISPR-modified pig kidney provided by eGenesis into Richard “Rick” Slayman, who later died of unrelated complications. Since then, Tim Andrews, who had similarly dismal prospects, received another of eGenesis’ xenotransplants, which enabled him to be taken off dialysis for the first time in over two years. Nine months later, the highest-risk period for both patients and transplants, he is still alive. Although Tim survived for 271 days with this kidney, doctors had to remove it after the organ’s function began to decline. Andrews will now resume dialysis and will remain on the list for a human donor kidney. Bill Stewart, the third and most recent recipient, has returned home and resumed work.
In February 2025, the FDA authorized eGenesis and another company to initiate clinical trials involving the transplantation of modified pig kidneys into individuals with end-stage kidney failure. In September 2025, the FDA cleared the company’s Investigational New Drug application to initiate a clinical trial evaluating the use of these pig kidneys. If successful in allowing long-term survival and relative health, this opens up a path to broader regulatory approval and provides hope to the nearly 550,000 patients currently on dialysis in the United States.
eGenesis doesn’t plan to stop with kidneys. In April 2025, they received FDA clearance for their IND application for a human-compatible, genetically engineered pig liver, offering a potential solution to an entirely different group of patients.
Fifteen years ago, all of the human health implications of the CCV grant weren’t immediately clear, but Tim Andrews, Bill Stewart, and soon others like them might not be alive today without that funding.
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