Xenotransplantation: Clinical Progress and a Need for Regulation
By CriShaun Hardy | December 18th, 2025
As of 2025, the global organ shortage remains a major public health issue. When last discussed on the Tox Blog, xenotransplantation, specifically the practice of using genetically modified pig organs in human patients, was examined for its scientific promise and for the profound biosafety, ethical, and regulatory questions that it raised. In the time since, the field has made major progress; it has gone from a speculative solution to active clinical trials, prompting the need to revisit these questions.
As xenotransplantation rapidly transitions to formal clinical trials, its scientific progress is outpacing the regulatory, ethical, and public-health frameworks that are needed for its safe and effective implementation.
Xenotransplantation Enters Clinical Trials
In November 2025, the first formal clinical trials of gene-edited pig kidneys transplanted into living human patients began. This marks a transition from isolated compassionate-use procedures to larger, systematic assessment. Under a compassionate use authorization, a patient facing a serious or immediately life-threatening condition is given special permission to receive treatments that have not yet undergone full FDA review and approval. The start of clinical trials thus marks a shift that acknowledges the potential approval of xenotransplantation as a clinically acceptable procedure. The clinical trials, conducted independently by United Therapeutics and eGenesis, involve a small number of patients facing end-stage renal disease (ESRD) who will receive a modified replacement kidney and be monitored for several years following the procedure to evaluate the success-rate of the replacement kidney.
In addition to the start of clinical trials for kidneys, genetically modified pig livers have also been greenlit by the FDA for an investigational new drug (IND) trial. Prior to this newly approved study, modified livers have shown some promise through an auxiliary transplant in 2024 and multiple transplants into brain-dead human recipients in early 2025. While this clinical trial has yet to begin, future success could expand the use of xenotransplantation in addressing acute organ failure cases more broadly.
Overall, this recent progress has been driven by increasingly advanced gene-editing processes. Companies conducting the modified pig kidney and liver trials state that the potential for xenotransplantation relies on their ability to “knock out” and replace unfavorable pig genes with human genes to reduce the chance of organ rejection in human patients.
The existence of multiple sponsors, increasingly standardized protocols, and movement towards coordinated oversight indicates that xenotransplantation is being positioned as a scalable clinical solution to the organ shortage. There are currently over 100,000 people on the U.S. transplant waiting list. Given the severity of the organ shortage, interest in alternative organ sources continues to grow.
Persistent Risks and Ethical Concerns
Despite optimism and advancing use, xenotransplantation still carries notable scientific, public-health, and ethical concerns. Even with extensive gene-editing, the long-term viability of xenotransplanted organs remains unclear. While immediate rejection was prevented in previous compassionate use trials, delayed rejection and organ failure remain major barriers. As of this post, the longest reported functioning genetically modified pig kidney in a human patient lasted approximately 9 months before being removed due to rejection. This surpassed the previous record where a modified pig kidney successfully functioned for 4 months before being rejected. While the long-term function of these organs in human hosts seems feasible, the eventual rejection demonstrates the need for further testing and a critical, more thorough examination of ongoing trials.
Another concern is the risk of zoonotic infection, particularly the potential activation or evolution of porcine endogenous retrovirus (PERVs). The activation of PERVs is a unique risk of xenotransplantation because it is present in the genome of all pigs and is an inherent risk where pig organs are introduced into human recipients. While gene-editing and the use of pathogen-free facilities to raise donor pigs reduce the risk of PERVs transmission across species, this risk has not been fully eliminated. Currently, no direct transmission of PERVs has been detected outside of in vitro studies, but long-term monitoring is necessary to determine the potential effect of PERVs presence.
In addition to these scientific and public health concerns, producing xeno-organs requires breeding, raising, and maintaining genetically modified pigs under intensely sterile conditions. Companies that operate in this space contend that their “designated pathogen-free facilities” utilize rigorous security and biosafety measures; however, there is little transparency as to the welfare of the pigs in these facilities. Concerns about animal welfare in this space are unique because the ethical implications of xenotransplantation extend beyond the traditional research-animal context. Large-scale xenotransplantation would, in effect, industrialize the use of animals for human organ harvesting. Existing animal-welfare frameworks were designed for laboratory operations rather than for biomanufacturing of organs. This scale of use would challenge these existing animal-welfare frameworks beyond their current capacity and raise significant questions about the ability to maintain an adequate level of welfare for these pigs.
Scientific Progress Outpacing Regulation
The field of xenotransplantation overlaps multiple regulatory areas, including biological products, animal research, public health monitoring, and transplant governance. Currently, regulatory authority over xenotransplantation is exercised by the FDA as the organs used in xenotransplants fall under the definition of “biological products” under the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act.
While the FDA has provided guidance documents for xenotransplantation in the context of infectious disease and industry development, there has been limited revision to these documents since their initial adoption in the early 2000s. As clinical activity increases and xenotransplantation products become more technologically sophisticated, regulatory stagnation may create uncertainties for clinicians and oversight bodies. The absence of more recent guidance, particularly regarding biosecurity and animal welfare, raises fundamental questions about whether existing guidance is adequate. Additionally, future policy will need to be updated to reflect current initiatives to phase out certain animal testing requirements to ensure that oversight keeps pace with scientific progress.
As xenotransplantation moves forward in formal clinical trials, greater consideration must be given to how future regulation and ethics will shape the evaluation of its feasibility and long-term integration into the organ transplantation framework.
The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.
