San Francisco, May 15, 2025 — Scientists at the University of California, San Francisco (UCSF) have taken a major step toward treating genetic disorders before birth by successfully delivering medicine directly into the amniotic fluid, a method that could help prevent irreversible damage caused by diseases like spinal muscular atrophy (SMA).
The study, published in Science Translational Medicine, shows that injecting therapeutic molecules into the amniotic fluid—a technique akin to an “inverse amniocentesis”—can safely and effectively reach developing fetal tissues, including the spinal cord. Researchers found that the treatment slowed or prevented nerve damage associated with SMA in mice, while demonstrating safety and drug distribution in a parallel sheep model.
SMA is a severe neurodegenerative disorder that causes progressive muscle weakness and often leads to death if left untreated. Though it can be diagnosed before birth, damage to the nervous system often begins in utero. The new research suggests that intervening during pregnancy may significantly improve outcomes.
A New Delivery Route for Genetic Therapies
The therapy uses antisense oligonucleotides (ASOs), short strands of synthetic DNA or RNA that modify how genes are expressed. ASOs are already used to treat infants and children with SMA and other nervous system disorders, but this study is the first to test delivery via amniotic fluid.
“Children with severe forms of SMA can have irreversible damage by the time they are born,” said Dr. Tippi MacKenzie, a fetal and pediatric surgeon at UCSF Benioff Children’s Hospitals and senior author of the study. “We wanted to see how we could treat as early as possible, in the least invasive way.”
In the mouse model of SMA, prenatal ASO treatment led to improved survival, better motor function, and greater numbers of motor neurons compared to untreated animals. In sheep—used to assess the safety of the technique—researchers observed that the ASOs reached therapeutic levels in multiple organs, including the spinal cord, without harmful side effects.
Safe, Effective, and Minimally Invasive
“This suggests we may be able to use amniotic fluid to deliver therapeutic RNA molecules for other severe, early-onset diseases that affect different areas of the body,” MacKenzie said.
The findings mark the first time researchers have tested the safety and systemic distribution of prenatal ASO delivery in large animals. Earlier studies explored intra-amniotic injection of ASOs in mice with genetic conditions such as Angelman and Usher syndromes, but this study is the first to combine safety and therapeutic efficacy across two animal models.
To advance toward human clinical trials, researchers must demonstrate both efficacy in correcting disease and acceptable safety data—both of which this study provides. The mouse data showed therapeutic benefit, while the sheep data confirmed wide distribution of the drug with no toxic effects.
Toward Human Trials
The research team now hopes to pursue clinical testing in humans.
“With these results, we are one step closer to testing prenatally in humans an existing treatment for those diagnosed with the disease,” said MacKenzie.
The procedure would be similar to an amniocentesis, where a needle is used to draw fluid from the amniotic sac to test for genetic disorders. However, in this case, the approach would deliver therapeutic agents rather than extract samples.
“This is sort of an inverse amniocentesis,” said Dr. Beltran Borges, the study’s lead author and a UCSF postdoctoral scholar specializing in pediatric neurology. “Once translated to the clinic, it could be an outpatient procedure.”
Medicine in Motion
One of the most surprising discoveries was how the medicine traveled throughout the fetus’s body. When ASOs were injected into the amniotic fluid, researchers observed through fluorescence imaging that the fetus swallowed and inhaled the medication, enabling distribution to various organs including the lungs, intestines, brain, spinal cord—and even nasal tissues.
“It is remarkable that you can inject something in the amniotic fluid, and over time a fetus swallows it or sniffs it in, and it gets to the brain and elsewhere,” Borges said. “There are likely other routes of entry as well, including through the bloodstream.”
A Collaborative Effort
The study reflects a significant collaborative effort between institutions and industry. UCSF led the sheep study with support from UC Davis, while mouse experiments were conducted in partnership with researchers from Johns Hopkins School of Medicine and Cold Spring Harbor Laboratory. Biotech firms Ionis and Biogen contributed crucial expertise, reagents, and experimental support.
“It takes a lot of trust and effort to put studies from three different labs and industry collaborators together,” MacKenzie said. “This type of multi-disciplinary collaboration—it’s the most rewarding way to do science.”
You Might Be Interested In:
- What to Do If You Have a Cough During Pregnancy?
- How to Manage Brown Discharge During Pregnancy?
- What to Do If You Have a Chemical Pregnancy?
