As global organ shortages persist, CRISPR-edited pig organs are emerging as a radical yet increasingly realistic solution to the crisis. Once hampered by immunological rejection and viral risks, xenotransplantation has entered a new era thanks to multiplex gene editing and encouraging early clinical results. This article examines the scientific rationale, major milestones, and leading players transforming theory into therapy. It also addresses the persistent barriers—from immune rejection to ethical debate—that must be resolved before CRISPR-edited organs become a routine clinical option. With scalable infrastructure, thoughtful regulation, and public trust, xenotransplantation may soon offer a future where no one dies waiting for an organ.
Rethinking the Organ Supply Crisis
Organ transplantation remains one of modern medicine’s most remarkable lifesaving interventions, yet it continues to be constrained by a severe and persistent shortage of available organs. In the United States alone, more than 100,000 people are currently on transplant waitlists, with a new patient added approximately every 10 minutes. Thousands die each year before a suitable donor can be found, and even successful recipients face long-term challenges such as immunosuppression and graft failure. These numbers are echoed globally, underscoring a structural mismatch between organ supply and demand that no amount of donor recruitment can fully resolve.
Against this backdrop, xenotransplantation — the transplantation of organs from non-human species into humans — has long held theoretical appeal as a way to create a renewable organ supply. Pigs have been a primary focus owing to their similar organ size and physiology, rapid reproduction, and potential for biosecure breeding. However, decades of efforts failed to advance beyond animal models or non-viable human trials, largely due to formidable immunological incompatibilities and the risk of cross-species viral transmission. Even with immunosuppression, organs from animals triggered violent immune reactions, and the threat of porcine endogenous retroviruses (PERVs) raised fears of introducing new zoonotic diseases.1
The emergence and subsequent maturation of CRISPR-based gene editing has reshaped what’s possible. By enabling the precise and efficient removal or modification of genes within the pig genome, CRISPR allows scientists to systematically strip away the molecular signals that trigger human immune rejection and to eliminate or suppress PERVs. Combined with advancements in transplantation protocols and preclinical testing, this technology has pushed xenotransplantation from the theoretical to the translational. For the first time, gene-edited pig organs are being successfully transplanted into living human recipients, marking the beginning of what could become a paradigm shift in transplant medicine.
Understanding the Science: Why Pigs? Why CRISPR?
The selection of pigs as the donor species for xenotransplantation is grounded in both biological and logistical rationale. Anatomically, pig organs are comparable in size and function to their human counterparts, making them suitable candidates for heart, kidney, liver, and even lung transplantation. Physiologically, their blood pressure, heart rate, and metabolic processes are sufficiently similar to humans to support functional compatibility after transplantation. Beyond biology, pigs can be bred in controlled environments with high biosecurity standards, allowing for large-scale and disease-free production of organs tailored for human use.2,3
Despite these advantages, the pig genome contains several components that provoke immediate and aggressive immune rejection when transplanted into a human. The most prominent culprits are carbohydrate antigens like alpha-gal and cytidine monophospho-N-acetylneuraminic acid (CMAH), which are absent in humans but prevalent in pigs. These molecules are recognized by the human immune system as foreign, leading to hyperacute rejection. Additional incompatibilities arise from differences in complement regulatory proteins and coagulation factors. Unedited, pig organs also carry a theoretical risk of transmitting PERVs — viruses integrated into the pig genome that can replicate under certain conditions, posing a zoonotic threat.4,5
To overcome these hurdles, researchers have turned to CRISPR/Cas9, a gene-editing tool that allows for the rapid, precise modification of multiple genomic sites simultaneously. Unlike earlier technologies, such as zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), which are more cumbersome and limited in scope, CRISPR enables multiplexed editing with greater efficiency and fidelity. Using CRISPR, scientists can knock out genes encoding xenoantigens and PERVs while simultaneously inserting human transgenes like CD46, CD55, and thrombomodulin to improve immune compatibility and reduce clotting risks.6
This multi-layered approach — removing immunogenic barriers, reducing viral risk, and enhancing tolerance — forms the backbone of the new generation of xenotransplantation protocols. It is not the use of pig organs per se that is revolutionary, but the ability to edit those organs into something that is not fully human, but no longer entirely pig.
Major Milestones in Xenotransplantation
Before the first CRISPR-edited pig organs were implanted in living humans, researchers spent decades refining xenotransplantation techniques through proof-of-concept studies in non-human primates and brain-dead human models. These preclinical experiments served as critical testing grounds for evaluating immunologic response, organ functionality, and the safety of gene-edited donor organs. In non-human primates, genetically modified pig kidneys and hearts achieved weeks to months of function, providing essential insight into compatibility and rejection pathways. More recently, transplanting pig organs into human patients with no brain activity allowed researchers to assess physiological integration under conditions closely mirroring clinical use, without the ethical and medical complexities of live-patient trials.7,8
These foundational studies laid the groundwork for a historic moment in early 2024, when Massachusetts General Hospital announced the first successful transplant of a CRISPR-edited pig kidney into a living patient. The recipient, Rick Slayman, had previously undergone a human kidney transplant that later failed, making him a candidate for this unprecedented procedure. The pig kidney was extensively modified to remove known rejection triggers and insert human-compatible proteins. Slayman’s post-operative course showed promising early graft function, though he passed away nearly two months later from causes not directly attributed to the transplant.9
Building on this momentum, other institutions initiated similar efforts. Tim Andrews became the second living patient to receive a CRISPR-edited pig kidney. Early reports suggested strong post-operative recovery and robust kidney performance, indicating progress in both surgical technique and immunological management.10 Another patient, Towana Looney, underwent transplantation with encouraging initial outcomes but ultimately experienced organ rejection, underscoring the persistent challenge of long-term graft survival even with intensive immunosuppressive regimens.11
These first-in-human procedures represent a turning point in the field. While they are not without complications, they demonstrate that CRISPR-edited pig organs can sustain life in human recipients — an achievement long thought out of reach. As researchers continue to refine gene edits, optimize surgical protocols, and develop more targeted immunosuppressants, each new case contributes to a growing body of clinical evidence, shifting xenotransplantation from an experimental frontier toward a viable medical practice.12
Leading the Xenotransplantation Revolution
The transition of xenotransplantation from the laboratory to the clinic has been accelerated by the concerted efforts of both commercial biotech firms and academic research centers. A handful of companies are leading the charge, leveraging CRISPR and related gene-editing technologies to develop transplant-ready pig organs at scale.
Among the most prominent is eGenesis, a company spun out of Harvard University that has consistently pushed the boundaries of gene editing in large animals. eGenesis has demonstrated extended survival of CRISPR-edited pig kidneys in non-human primates and recently supported one of the highest-profile cases of successful pig kidney function in primates for over two years, an unprecedented benchmark that brought the company international recognition.13 Their platform integrates over 60 genetic modifications to eliminate xenoantigens, suppress viral transmission, and enhance immune compatibility — representing one of the most sophisticated gene-editing programs in the field.14
United Therapeutics has taken a different yet complementary approach, focusing on the infrastructure required to industrialize xenotransplantation. The company is currently developing a $96 million facility in Houston dedicated to breeding and maintaining genetically modified pigs under strict biosecurity protocols. This investment reflects a long-term commitment to making gene-edited organs a reliable and regulated part of the transplant ecosystem, with ambitions to eventually supply a range of organ types, including hearts and lungs.15
Other players such as Makana Therapeutics and Revivicor are also contributing key innovations, from proprietary gene-edited pig strains to novel transplantation protocols. These companies are not operating in isolation but often collaborate with transplant surgeons, immunologists, and regulatory bodies to advance the field collectively.
In parallel, academic institutions remain foundational to the progress of xenotransplantation. NYU Langone, the University of Alabama at Birmingham, and Massachusetts General Hospital have all played central roles in performing first-in-human trials and refining the clinical parameters of success. These centers not only conduct transplant procedures but also lead longitudinal studies on graft function, immune response, and patient outcomes.
The Harvard Wyss Institute continues to advance the science through its deep expertise in synthetic biology and multiplex genome engineering. Their research pipeline focuses on developing pigs with customized genetic profiles to meet specific clinical needs, combining CRISPR with other gene-editing tools to optimize organ compatibility and reduce rejection.3
Together, these industry and academic actors are building the foundations of a future xenotransplantation ecosystem: one that is not merely scientifically feasible but logistically and commercially sustainable.
Barriers to Overcome
Despite major scientific and clinical milestones, xenotransplantation remains an experimental therapy facing substantial biological, safety, and ethical challenges. These hurdles must be addressed systematically before widespread clinical implementation becomes a reality.
Immunological rejection remains the most immediate and persistent obstacle. Hyperacute rejection, which occurs within minutes of transplantation, is triggered by preformed human antibodies recognizing pig-specific carbohydrate antigens, such as alpha-gal, leading to rapid graft destruction. Even when hyperacute responses are mitigated through gene editing and immunosuppression, chronic rejection can emerge over time, driven by cellular immune responses, antibody development, and inflammatory pathways. In addition, transplanted pig organs are prone to microvascular thrombosis and clotting abnormalities in the human host due to mismatches in coagulation regulation, which can lead to graft dysfunction or failure.16
These immunologic risks require the use of intensive immunosuppressive regimens. While effective in the short term, such regimens increase patient vulnerability to infections, malignancies, and metabolic disorders. The goal of inducing long-term tolerance without life-long immunosuppression remains elusive, and new approaches will be needed to achieve safer and more durable outcomes.1
Another area of concern is the potential for zoonotic infection, particularly from PERVs, which are embedded in the pig genome. Though these viruses have not yet been shown to cause disease in humans, their presence represents a theoretical risk that has historically delayed regulatory acceptance of xenotransplantation. Advances in CRISPR have made it possible to delete or inactivate all copies of PERVs in donor animals, significantly reducing the risk, but long-term surveillance of recipients will still be required to monitor for unforeseen viral activity.17
Beyond the scientific and clinical domains, xenotransplantation raises complex bioethical questions. The use of pigs — highly intelligent and sentient animals — for organ harvesting prompts debate over animal rights and welfare, especially when animals are genetically modified and bred for the express purpose of being sacrificed for human use. There are also broader philosophical concerns about the implications of crossing species boundaries, particularly when organs are engineered to be part-human in function or composition. These questions are amplified by the need to ensure equitable access to future xenografts. Without careful policy planning, xenotransplantation could widen global disparities in access to transplantation, especially if early successes are commercialized at prohibitive cost or subject to restrictive regulatory frameworks.
In this next phase of development, solving the scientific and clinical challenges will not be sufficient on their own. Progress will also depend on building a system that balances innovation with responsibility, inclusivity, and transparency.
From Compassionate Use to Clinical Norms
As xenotransplantation moves from experimental surgery into regulated clinical practice, the role of regulatory agencies has become increasingly pivotal. In the United States, the Food and Drug Administration (FDA) has taken a cautiously progressive stance. While the agency had long regarded xenotransplantation as high risk due to concerns about immune rejection and zoonotic infection, recent advances in gene editing and preclinical safety data have prompted a shift toward conditional approval pathways. In early 2025, the FDA authorized the first formal clinical trials of genetically modified pig kidneys in living human recipients, marking a significant milestone in the regulatory acceptance of this technology.12
These initial trials are governed by stringent protocols designed to mitigate known risks. Candidate patients are typically those for whom no human donor organ is available and for whom the risks of continuing without a transplant outweigh those of experimental intervention. Trial participants are closely monitored under comprehensive safety frameworks that include real-time assessments of graft function, immune response, and viral activity. To date, trials have been structured under expanded access or compassionate use provisions, but there is growing discussion about how to evolve these frameworks into broader, multi-center clinical studies.18
Internationally, regulatory approaches vary widely. While the United States is emerging as a leader in clinical deployment, other countries have been more conservative or are still in early stages of guideline development. In Europe, xenotransplantation remains subject to strict oversight, with ethical and biosafety considerations still under review. In Asia, where some initial pig liver transplants have already been conducted in brain-dead or non-survival models, regulators have shown a willingness to explore limited trials under highly controlled conditions. The fragmented nature of global policy highlights the need for international collaboration and harmonization of standards, especially as gene-edited organ manufacturing scales across borders.19
Establishing clear and consistent clinical and regulatory pathways will be critical to expanding patient access and building public trust. Beyond approval, ongoing transparency in data sharing, long-term patient monitoring, and postmarket surveillance will be essential to ensure that early success stories are followed by sustained clinical benefit and safety.
Looking Ahead: The Road to Routine Use
The current state of xenotransplantation reflects a remarkable leap from theoretical possibility to clinical feasibility, but routine use remains on the horizon rather than within reach. The handful of CRISPR-edited pig kidney transplants performed in living patients have demonstrated short-term survival of weeks to months, with encouraging early organ function and manageable complications. However, consistent long-term success — defined by durable graft survival, minimal immune complications, and sustained quality of life — has yet to be fully established. These first cases are critical proofs of concept, but they also underscore the need for broader trials involving more diverse patient populations and longer follow-up durations.8
In the meantime, CRISPR-edited pig organs are beginning to serve as important tools in bridging therapies. Pig kidneys are being integrated into treatment regimens for patients undergoing dialysis, offering temporary support while human organs remain unavailable. Similarly, liver xenografts — engineered for metabolic rather than full hepatic function — are being explored for use in acute liver failure cases where conventional transplantation may not be possible. These partial-function or short-term applications could represent a steppingstone toward more ambitious, long-term use.7
Looking forward, several areas are poised to shape the next phase of development. One of the most urgent is the extension of xenotransplant trials to pediatric patients. Children face even greater challenges in organ transplantation owing to their size, immune status, and growth needs. Success in adult patients could open the door to using smaller pig organs in younger recipients, though such applications will require additional safety data and ethical review.
Another priority is the industrialization of xenograft manufacturing. Producing genetically edited pigs at scale under tightly controlled, biosecure conditions is a logistical and economic challenge. Companies like United Therapeutics are already investing in large-scale facilities, but further innovation will be needed to bring down costs, standardize quality, and ensure accessibility across health systems.20
Beyond whole-organ transplantation, researchers are exploring combination strategies that merge gene-edited animal organs with human cellular components. For example, bioartificial organs seeded with a patient’s own cells could reduce the need for immunosuppression, while hybrid platforms might allow for therapeutic applications even before full xenotransplantation becomes routine. These approaches point to a future where xenotransplantation is not merely a stopgap for organ shortages, but a flexible, programmable platform for regenerative medicine and personalized care.
The path to routine use will demand not just scientific innovation, but also scalable infrastructure, regulatory clarity, and public trust. With each step forward, the vision of a reliable, renewable source of transplantable organs draws closer to clinical reality.
The Future Is Editable
The last decade has witnessed extraordinary progress in the science of xenotransplantation, driven by breakthroughs in genome editing, preclinical modeling, and early human trials. What was once a speculative concept — using gene-edited pig organs to treat human disease — has now entered the realm of clinical possibility. CRISPR-enabled manipulation of the pig genome has addressed many of the historical roadblocks to compatibility and safety, and the successful transplantation of kidneys into living human recipients marks a milestone not only in medicine but in the broader application of synthetic biology to human health.
Yet, much work remains before xenotransplantation can fulfill its transformative promise. Long-term outcomes, immunological tolerance, infection risk, and ethical considerations continue to shape the contours of what’s possible and acceptable. The field must also demonstrate that these advances can scale clinically, economically, and equitably so that the benefits of organ replacement are not confined to experimental settings or privileged access.
Still, the vision is compelling: a world where the availability of organs no longer dictates the fate of patients with end-stage disease. Where organ transplants are not rationed but routinely offered. Where children and adults alike no longer die waiting for a match that may never come.
Achieving this future will require sustained effort across multiple domains. Regulatory frameworks must evolve to support innovation while ensuring safety and ethical oversight. Investment in infrastructure—from breeding and genetic engineering to clinical delivery—must keep pace with scientific progress. And public engagement will be essential to building trust, addressing concerns, and ensuring that these advances are implemented in a just and inclusive manner.
The era of CRISPR-edited xenotransplantation has begun. Whether it becomes a cornerstone of 21st-century medicine will depend on the collective will to move from possibility to practice. The opportunity is historic, and the responsibility is urgent.
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