For Immediate Release: Wednesday, October 21, 2026, 1:40 p.m. U.S. Eastern Time
Media Contact: Evelyn Mantegani, +1 240-833-2014, [email protected]
Presented By: Xiaona Lu, MD, PhD, Yale School of Medicine
Gene editing could transform treatment for neurological genetic disorders, but delivering gene-editing tools broadly throughout the brain remains a major challenge. Researchers have developed a nonviral CRISPR delivery platform that reactivated the gene deficient in Angelman syndrome across preclinical models, including nonhuman primates.
The Stimuli-Responsive Traceless Engineering Platform, or STEP, uses chemical modifications to deliver CRISPR-Cas9 gene-editing components without viral vectors or lipid nanoparticles. Its small size may support broad distribution in the brain, while transient exposure to Cas9 may help limit unintended editing.
Researchers tested STEP in animal models of Angelman syndrome, a severe neurogenetic disorder caused by deficient expression of the maternal UBE3A gene in neurons. Although the paternal copy of UBE3A is intact, it is normally silenced by an antisense RNA transcript. In patient-derived brain organoids and mouse models, a single STEP treatment disrupted this transcript and reactivated paternal UBE3A. Treated mice also showed improvements across neurobehavioral and brain-wave measures.
In nonhuman primates, imaging demonstrated broad brain distribution following administration into the fluid surrounding the brain and spinal cord. STEP reactivated paternal UBE3A expression across the brain that are significantly more efficient than previously reported for antisense oligonucleotide approaches in nonhuman primates.
The research remains preclinical, and dose-ranging toxicology studies in nonhuman primates are ongoing. If further studies establish safety and effectiveness, STEP could offer a potential strategy for treating Angelman syndrome and a broader platform for delivering gene-editing therapies throughout the brain.
About the American Society of Human Genetics (ASHG)
The American Society of Human Genetics (ASHG) is the leading global organization advancing the science of human genetics and genomics. Representing nearly 8,000 researchers, clinicians, genetic counselors, educators, and other professionals, ASHG drives progress in understanding the human genome and its role in health and disease. The Society fosters innovation and collaboration through its flagship events and publications—including the ASHG Annual Meeting and its peer-reviewed journals The American Journal of Human Genetics and Human Genetics and Genomics Advances. ASHG also champions science advocacy, supports the next generation of genetics professionals, and promotes responsible policies and public engagement in genetics. Learn more at www.ashg.org.
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