For the scientific enterprise, 2025 was marked by setbacks and challenges. But scientists are no strangers to adversity—the ability to overcome obstacles is built into our training. In turn, research labs across the country found ways to keep discovery moving forward. As a result, 2025 delivered some of the most influential science stories of the decade. In this special section, GEN editors look back at 2025 to highlight six of the biggest stories of the year—moments that not only reshaped fields but also demonstrated the resilience and determination driving scientific research.
FDA and Sarepta Grapple with Response to Elevidys Deaths
The deaths of three Duchenne muscular dystrophy (DMD) patients receiving Sarepta Therapeutics’ marketed treatment Elevidys® (delandistrogene moxeparvovec-rokl)—and the abrupt responses of the U.S. Food and Drug Administration (FDA)—reignited the longtime issue of gene therapy safety this year.
A 16-year-old male succumbed in March to acute liver failure after being dosed with Elevidys, the only gene therapy to win FDA approval as a DMD treatment. Three months later, a second Elevidys patient of undisclosed age died. As both patients were non-ambulatory, Sarepta halted shipments of Elevidys for non-ambulatory patients and paused the Phase III ENVISION trial (NCT05881408).
Following a third death, that of an 8-year-old Brazilian boy, the FDA demanded Sarepta pause shipments of Elevidys to ambulant patients. Sarepta initially refused before agreeing on July 21. A few days later, the FDA reversed itself, recommending that Sarepta resume Elevidys shipments to ambulant patients, after Brazilian authorities ruled out treatment with the gene therapy as a factor in the boy’s death.
The confrontation reflected a more conservative approach to regulating drugs and approval applications by Vinay Prasad, MD, director of the FDA’s Center for Biologics Evaluation and Research. The FDA changed course on Sarepta, according to news reports, following pleas to Congress, the FDA, and President Donald Trump by conservative leaders and DMD patient advocates, who launched a Change.org petition. Prasad resigned on July 29 but returned to his FDA post on August 9.
The FDA’s database also reveals two additional deaths of Elevidys patients. Sarepta said those deaths were unrelated to their use of the gene therapy.
Baby KJ Provides a Glimpse of Tailor-Made Medicine
In May 2025, the world met “Baby KJ,” the first patient treated with a fully personalized, in vivo CRISPR therapy—an N-of-1 therapy led by a team at the Children’s Hospital of Philadelphia. Working together with academia, industry, and governmental partners, the team developed a bespoke mRNA-based CRISPR therapy targeting KJ’s unique mutation in the carbamoyl phosphate synthetase I (CPS1) gene.
“We need a patient-first approach for any variant in any patient, whomever, wherever they are. Each and every patient deserves a fair shot at this,” announced Kiran Musunuru, MD, PhD, professor for Translational Research at the Perelman School of Medicine at the American Society of Gene & Cell Therapy (ASGCT) meeting in May of this year.
The achievement demanded a coordinated sprint under intense timelines. Teams at IDT, Aldevron, Danaher, Acuitas Therapeutics, and others came together to deliver the gene‑editing payload and its delivery system, marking an unprecedented collaboration in the world of CRISPR therapies. Baby KJ’s case has not only become a blueprint for the future of personalized genome editing, but it also spotlights a critical bottleneck: scalability. Delivering individualized therapies to more than a handful of patients will demand modular, automated bioprocessing platforms, digital documentation pipelines, and flexible regulatory pathways that can handle micro-batches of one.
This moment is a call to reimagine how medicine meets the individual. To help meet that challenge, new alliances are forming. The Innovative Genomics Institute and Chan Zuckerberg Initiative launched the Center for Pediatric CRISPR Therapies, and industry partners are investing in next-generation manufacturing hubs. As Fyodor Urnov, PhD, professor of Molecular Therapeutics at UC Berkeley and a director of Technology & Translation at the Innovative Genomics Institute, noted, “There is so much innovation on the way … to help the next Baby KJ.”
Boltz-2 and the Open-Source Future of Drug Discovery
By Fay Lin, PhD
In June, researchers from the Massachusetts Institute of Technology (MIT) Jameel Clinic for Machine Learning in Health, in collaboration with AI biotech company Recursion, announced the open-source release of Boltz-2, which now predicts molecular binding affinity at newfound speed and accuracy, to help “democratize” commercial drug discovery. The model is available under a highly permissive license from MIT that allows commercial use.
Binding affinity is an experimental measure of the strength of interaction between a drug and its target and is a key drug discovery metric that can dictate the progression of a candidate through the early drug discovery and development pipeline. Given that such experiments can cost hundreds or thousands of dollars per individual molecule, cost savings can come from applying Boltz-2 to cut down on the time and number of experimental rounds needed to advance a drug candidate.
In accuracy, Boltz-2 was the leading affinity performer at the December 2024 Critical Assessment of protein Structure Prediction 16 (CASP16) competition, the biannual experiment that assesses the latest state-of-the-art models in structural biology. In speed, Boltz-2 is reported to calculate binding affinity values in just 20 seconds, 1000x times faster than the current physics-based computational standard, free-energy perturbation (FEP) simulations.
“Just at a time where it seemed inevitable that closed models like AlphaFold3 would dominate the field, many researchers from academia and industry decided to contribute to an open-source project like Boltz to build new capabilities and open them up for everyone to use,” said Gabriele Corso, PhD, one of the Boltz developers at MIT.
The Cell and Gene Therapy Rollercoaster
Few biotech commentators were familiar with Hy’s Law until Intellia voluntarily paused its clinical trial in October because an 80-year-old trial volunteer was hospitalized with serious liver enzyme elevation. As the industry scrambled to understand the pathogenesis of this adverse event, Intellia investors fled while the FDA issued a clinical hold. The patient has since died.
Just one month earlier, the field was celebrating remarkable clinical data released by UniQure. Investigators in London reported preliminary results in a gene therapy trial for patients with the incurable adult-onset Huntington’s disease, in which an RNA construct injected with meticulous precision directly into the patient’s brain halted and, in some cases, reversed symptoms. But the FDA squashed that enthusiasm in November by moving the endpoint goalposts; UniQure shares plummeted 60% on the news.
The potential of cell and gene therapy was discussed earlier this year in an extraordinary roundtable hosted at FDA headquarters, following on the heels of the “Baby KJ” story (see p19). David Liu, PhD, told FDA leadership that the community could use bespoke gene editors to treat up to 1,000 children with rare genetic disorders. The FDA subsequently included just one gene therapy (for hereditary deafness) among the nine programs awarded the FDA’s National Priority vouchers.
Uptake of the first CRISPR-based medicine is steadily picking up pace: Vertex recently disclosed that some 165 people with sickle cell disease or thalassemia have had their stem cells harvested in preparation for treatment with Casgevy, while 39 have received treatment. Cell and gene therapy remains an exciting field showcasing innovative science and delivery systems, but the path to securing approval remains difficult.
How NIH Budget Cuts Threaten American Science
By Uduak Thomas
Perhaps one of the most consequential decisions of this year was the U.S. government’s decision to significantly slash funding for scientific research supported by the National Institutes of Health (NIH). According to one estimate from a Massachusetts Institute of Technology (MIT) and Johns Hopkins University (JHU)-led study, the current administration cut upwards of 40% of NIH research funding and has a proposed budget for the 2026 fiscal year that includes an additional 39% cut to the agency’s budget.1
It is an alarming shift considering the contributions of NIH-funded studies to the discovery of hundreds of approved drugs and vaccines in the past few decades. As an example of the kind of impact a decision like this could have, that same study from MIT and JHU found that “more than half of the drugs approved by the FDA since 2000 are connected to NIH research and would likely have been cut under a 40% budget reduction.”
Less than a year into the current administration, the funding cuts are already straining universities, research centers, and core laboratories as PhD programs rescind student offers and shelve planned studies and trials. Scientists across the country have been calling on the administration to protect the future of biomedical research, starting with the Stand Up for Science marches2 and a letter signed by over 1,200 scientists asking NIH Director Jay Bhattacharya MD, PhD, to restore cut research grants.3 But without concrete action, the cuts risk slowing the development of vital drugs, therapies, and vaccines that could save lives now and in the future.
Eight Healthy Babies Born via Pronuclear Transfer Bring Hope for Mitochondrial Disease
This past summer brought a breakthrough that offers new hope to families affected by mitochondrial disease. Eight babies—born to women at high risk of transmitting serious disease caused by mutations in their mitochondrial genomes—showed no signs of mitochondrial disease thanks to pronuclear transfer. All eight babies, ranging in age from 0 months to over 24 months, were deemed healthy at birth and were described as developing normally.
Pronuclear transfer, which was first described in 2010, involves transplanting the nucleus from an egg carrying a mitochondrial DNA mutation to an egg donated by an unaffected woman that has had its nuclear genome removed. The resulting embryo inherits its parents’ nuclear DNA, but the mitochondrial DNA is inherited predominantly from the donated egg.
During the follow-up of this trial, all the babies met their relevant developmental milestones. The authors say that any other health conditions of the children were not thought to be related to the maternal
mitochondrial DNA mutations.
How did the team feel about the results? “It’s reassuring. Absolutely,” asserted Bobby McFarland, PhD, director of the NHS Highly Specialised Service for Rare Mitochondrial Disorders and professor of Pediatric Mitochondrial Medicine at Newcastle University. In the past, it has been difficult to provide advice to people with mitochondrial disease. But now, he notes, a picture is emerging that provides enough information so that people can make informed decisions. And with these data comes cautious optimism. To see these babies now—and to know that they are not going to have mitochondrial disease—is “just amazing,” he said.
References
1. NIH Funding Cuts’ Impact on Drug Discovery and Development.
2. Scientists in NYC Rally to Defend and Stand Up for Science.
3. Scientists Urge NIH Director to Restore Research Grants Halted by Trump Administration.
