The Organ Crisis Is Over – Thanks to These 25 Genetic Transformations in Pigs

Home Animals The Organ Crisis Is Over – Thanks to These 25 Genetic Transformations in Pigs

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The Organ Crisis Is Over – Thanks to These 25 Genetic Transformations in Pigs

By Chu E. - April 27, 2025

The global organ shortage has pushed scientists to find new solutions, and pig organs might be the answer we need. Through advanced genetic engineering, researchers have transformed pig organs to work in human bodies. These modifications tackle the main problems that prevented successful cross-species transplants before. Let’s explore the fascinating genetic changes making pig organs compatible with humans.

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Eliminating the Alpha-Gal Problem

The Organ Crisis Is Over – Thanks to These 25 Genetic Transformations in Pigs — Source: mdpi.com

Scientists used CRISPR-Cas9 to delete the GGTA1 gene in pigs. This gene makes alpha-gal sugar, which triggers immediate rejection in humans. Without this gene, pig organs avoid the first major hurdle of transplantation. Tests in 2021 showed these modified pig kidneys working in brain-dead humans for up to 72 hours without the typical immediate rejection response. The simple genetic deletion makes a profound difference in compatibility, opening new doors for organ availability.

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Fighting Hidden Viral Threats

In 2017, eGenesis disabled 62 porcine endogenous retroviruses (PERVs) in pig cells. They edited pig fibroblast genomes precisely, then used nuclear transfer to create PERV-free pigs. This was no small task. The breakthrough tackled a major safety concern about viral transmission between species. Now doctors can transplant pig organs with less worry about passing unknown viruses to human recipients. The extensive editing process required meticulous verification to ensure complete viral inactivation.

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Human Shield Proteins

Pigs now carry human genes CD46, CD55, and CD59, which block the complement system from attacking foreign tissue. Scientists added these genes using viral vectors to ensure stable expression in pig organs. The results speak for themselves. In primate studies, these genes extended graft survival by up to six months by protecting against the complement system’s destructive effects. These human proteins act like molecular shields, confusing the recipient’s immune system into accepting the foreign tissue.

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Long-lasting Kidney Transplants

eGenesis created pig kidneys with 10 genetic edits in 2023. Their kidneys kept monkeys alive for over a year. These kidneys showed normal function with no rejection signs when paired with immunosuppression drugs. This success wasn’t just a lab curiosity. It marked a turning point toward human trials by proving these organs could work long-term in primates. The kidneys filtered blood and produced urine consistently throughout the study, demonstrating remarkable functional stability.

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Simple Changes Work Too

NYU Langone’s 2023 study showed that even one genetic change makes a difference. They transplanted a pig kidney with only the alpha-gal gene knocked out into a brain-dead human. The kidney worked for 32 days. This suggested that sometimes less is more. Simple modifications might still create viable organs without complex engineering, opening up faster paths to clinical use. The kidney maintained normal filtration rates under standard immunosuppression protocols, producing clear urine throughout the test period.

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Preventing Blood Clots

Scientists added human thrombomodulin to pig organs to prevent dangerous blood clots. Using a lentiviral vector, they ensured expression in pig blood vessel cells. This change made a big difference. Pig-to-baboon heart transplants lasted weeks longer because the human protein reduced clot formation. Blood clotting problems had previously doomed many xenotransplant attempts. The protein works by interfering with the coagulation cascade at key points, keeping blood flowing smoothly through the newly transplanted organ.

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Eliminating Viral Risks

CRISPR technology helped researchers target and remove more pig retrovirus genes beyond PERVs. Whole-genome sequencing confirmed the edits worked, showing no viral activity in the modified cells. These extra safety steps matter. They address regulatory concerns and make pig organs safer for human recipients by reducing infection risks that could derail clinical progress. Researchers meticulously verified each edit to ensure no unintended changes occurred elsewhere in the genome during the modification process.

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Heart Transplant Breakthrough

The University of Maryland made history in 2022 by transplanting a modified pig heart into a living human. The heart had 10 genetic modifications and functioned for 60 days with experimental drugs. This wasn’t just a scientific milestone. The procedure showed pig hearts could potentially serve as a bridge or permanent solution for patients waiting for human donors. The patient, who would have died without intervention, received precious additional time with his family thanks to this pioneering procedure.

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Targeting Additional Antigens

The B4GALNT2 gene produces another problematic sugar that triggers rejection. Scientists disabled this gene using CRISPR, reducing antibody binding by 70% in lab tests. This change works with alpha-gal removal to create a better organ. Together, these modifications greatly lower the risk of acute organ rejection after transplantation. The combination approach proves especially effective because it addresses multiple aspects of the immune response simultaneously, creating a more comprehensive defense against rejection.

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Better Blood Flow Engineering

Human coagulation factors EPCR and TBM were added to pig genomes to improve blood flow in transplanted organs. These genes appeared in pig blood vessels through transgenic methods. The results proved impressive. Baboon studies showed a 50% drop in transplant failures from blood clots, solving another major obstacle to successful xenotransplantation. The modification targets the interface between the organ and recipient blood, where dangerous clots typically form during the critical first days after surgery.

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Teaching the Immune System Tolerance

Pig kidneys received embedded thymus glands to help recipients tolerate the foreign organ. The thymus tissue trains human T-cells to accept pig cells as “self” rather than foreign. This clever approach works well. In 2024 studies, this technique extended pig kidney survival in primates beyond 200 days by reducing delayed rejection responses. The thymus gland acts like a training school for immune cells, teaching them to recognize and accept the new organ rather than attacking it as they normally would.

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Record-Breaking Kidney Editing

eGenesis pushed boundaries in 2024 with a pig kidney containing 69 CRISPR edits. This kidney worked for weeks in a brain-dead human with minimal anti-rejection drugs. Such extensive editing wasn’t just for show. It demonstrated how precise and scalable modern gene-editing technologies have become, allowing multiple changes to create truly compatible organs. The test validated that dozens of simultaneous genetic modifications could function together without compromising the organ’s essential operations or creating unexpected problems.

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Alternative Editing Methods

Scientists used TALENs instead of CRISPR to knock out the GGTA1 gene in miniature pigs. These pigs showed 90% less human antibody binding compared to normal pigs. This success matters. It validated TALENs as another tool for xenotransplantation modifications, giving researchers options when certain genes prove difficult to edit with CRISPR. Having multiple editing technologies available helps scientists overcome specific technical challenges that might arise with particularly stubborn genes or when precise control is needed.

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Self-Protecting Organs

Pigs now produce CTLA4-Ig, a protein that blocks T-cell activation and reduces rejection. Scientists delivered this gene via adenoviral vectors to achieve high expression. The results proved significant. In primate studies, these kidneys survived up to 100 days longer than control organs, showing how organs can carry their own anti-rejection protection. The protein specifically interrupts the communication between immune cells that would normally coordinate an attack on the foreign tissue, like cutting the telephone lines before an invasion.

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Liver Support Systems

Penn Medicine connected a gene-edited pig liver to a brain-dead human in January 2025. The liver had 12 genetic modifications and functioned for 72 hours without rejection. This test wasn’t a full transplant. Instead, it advanced the prospect of temporary liver support for patients waiting for human organs or recovering from liver failure. The liver successfully processed toxins and produced essential proteins throughout the test period, demonstrating its potential as a bridge therapy.

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Triple Antigen Knockout

Revivicor created pigs lacking three key antigens: alpha-gal, B4GALNT2, and CMAH. Lab tests showed these organs bound 85% fewer human antibodies. These special pigs now serve important roles. They’re used in FDA-approved xenotransplantation research, bringing us closer to clinical use of pig organs in humans who need them. The triple knockout approach addresses multiple rejection pathways simultaneously, creating a more comprehensive solution than single-gene modifications alone could provide.

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Complement System Defense

Pig organs expressing human CD46 degrade C3b and C4b proteins, stopping the complement cascade. Scientists used a piggyBac transposon system for stable gene integration. The impact was clear. Pig-to-baboon kidney transplants with CD46 lasted twice as long as unmodified organs, showing how human proteins can protect against specific rejection mechanisms. The CD46 protein acts at a critical junction in the complement pathway, essentially disarming this powerful immune weapon before it can damage the transplanted tissue.

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Size-Appropriate Organs

Researchers knocked out the growth hormone receptor gene in pigs to control organ size. This prevented overgrown organs that wouldn’t fit human anatomy. By 2023, these pigs produced kidneys perfectly sized for adult humans. Size matching matters. It helps avoid complications like organ hypertrophy that could derail otherwise successful transplants. The modification ensures the organs grow to an appropriate size while maintaining normal function, addressing practical concerns about anatomical compatibility between species.

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FDA Regulatory Milestone

The FDA approved GalSafe pigs in 2020 for human therapeutics and food use. Revivicor created these alpha-gal-free pigs using homologous recombination. This approval wasn’t just about these specific pigs. It established an important regulatory precedent for using genetically modified pigs in medical applications, paving the way for future approvals. The decision involved extensive safety testing and set critical standards for how genetically modified animals would be evaluated for human medical use.

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Burn Treatment Innovation

Massachusetts General Hospital used gene-edited pig skin on a burn patient in 2019. The skin lasted five days, integrating with human tissue without rejection. This success wasn’t limited to organ transplantation. It highlighted how pig-derived tissues could help in emergency medicine, offering new options for severe burn patients needing immediate coverage. The pig skin provided protection from infection and fluid loss while giving the patient’s own skin time to heal underneath.

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Diabetes Treatment Progress

Chinese researchers transplanted modified pig insulin-producing cells into diabetic patients in 2024. The cells restored insulin production for up to six months with mild immunosuppression. These results offer hope. The trial showed xenotransplantation’s potential beyond whole organs, potentially helping millions with endocrine disorders like diabetes. The patients required significantly less external insulin, and some experienced periods where they needed none at all, suggesting the transplanted cells functioned effectively.

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Reducing T-Cell Rejection

Pig livers modified to express PD-L1 survived in baboons for 29 days. Scientists used CRISPR knock-in techniques to target liver cells specifically. This change addressed a critical issue. It reduced T-cell-mediated rejection, one of the biggest challenges in xenotransplantation after the initial barriers are overcome. The PD-L1 protein binds to receptors on T-cells, sending them a “stand down” signal that prevents them from attacking the transplanted organ’s cells.

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Small Pigs for Better Matching

TALENs created GGTA1-null miniature pigs with organs better suited for human transplantation. These pigs showed no alpha-gal expression and less reactivity with human blood. Their smaller size offers advantages. Their organs fit better in pediatric patients or smaller adults, expanding the potential recipient population for these modified organs. The compact organs also require less blood supply to function properly, making them potentially easier to integrate into the human circulatory system.

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Growing Human Organs in Pigs

Scientists integrated human stem cells into pig embryos lacking organ-forming genes. By 2023, they developed chimeric embryos with human kidney precursors surviving 28 days. This approach takes a different path. It could eventually produce fully human organs inside pigs, completely avoiding rejection issues rather than just reducing them. The chimeric embryos contained specific target organs composed mostly of human cells, while the rest of the developing animal remained predominantly porcine.

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Clinical Trials Begin

The FDA authorized clinical trials for gene-edited pig kidneys in March 2025. These kidneys have up to 12 modifications and will be tested in patients with end-stage renal disease. This authorization marks a turning point. It represents a crucial regulatory milestone for bringing xenotransplantation into mainstream clinical medicine. The trials, led by eGenesis and Revivicor, plan to enroll patients who otherwise have limited options due to organ shortages or compatibility issues.

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Hope for the Future

These genetic engineering achievements bring pig organs closer to widespread human use. While challenges remain around long-term immunosuppression and ethical questions, the organ shortage crisis may soon have a solution. Ongoing clinical trials will determine if xenotransplantation becomes standard medical practice. Many patients on transplant waiting lists now have reason for new hope thanks to these remarkable scientific advances. As researchers continue refining these techniques, the dream of unlimited organ availability inches closer to reality.

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