Ученые из Университета Иллинойса создали инструмент для лечения болезни Хантингтона

To subscribe, click here URBANA — University of Illinois researchers have developed a gene-editing tool that reduces toxic protein buildup in mice with Huntington’s disease, offering a potential blueprint for treating the fatal brain disorder in humans. Led by bioengineering Professors Thomas Gaj and Pablo Perez-Pinera, the team engineered a molecular tool known as an adenine base editor. The tool alters how cells process instructions for producing huntingtin, a protein vital to brain function that turns toxic in Huntington’s patients. Rather than shutting the gene down entirely, the editor acts like a precise red pen. It rewrites a small segment of genetic code, so cells bypass a critical cut site, preventing the protein from breaking apart into toxic fragments. “The treatment reduces the toxic protein fragments more strongly than it reduces full-length huntingtin,” Gaj said. “Importantly, this approach does not selectively target the mutated gene. Instead, it targets both the mutant and healthy gene and creates a version that cannot be processed to generate toxic byproducts but still retains important functions.” Huntington’s disease is a genetic condition that damages nerve cells over time, causing involuntary movements, loss of motor control, and cognitive decline. Since the UI team’s tool targets a universal sequence shared by both healthy and mutated huntingtin genes rather than a patient-specific mutation, Gaj noted the approach could work across a broad spectrum of patients. To deliver the genetic editor into the brain, researchers used adeno-associated virus serotype 9, or AAV9. In gene therapy, AAV9 acts like a microscopic delivery truck — a harmless virus engineered to pass into brain tissue and drop off genetic payloads inside cells. Because the base editor was too large to fit inside a single viral truck, researchers split the package across two vectors and injected them directly into the striatum, the brain region responsible for movement control, which suffers heavy damage in Huntington’s patients. In testing, the editing tool reduced toxic protein fragments by roughly 60 percent and cut clumped protein deposits by 63 percent in the targeted area. Those cellular changes led to physical improvements in the test subjects. At 1 year old, treated mice demonstrated a 52 percent increase in grip strength, a 48 percent improvement on a rotating rod test that measures balance and agility, and a 38 percent reduction in abnormal limb folding, a common sign of neurological decline. Because researchers did not conduct learning or memory tests, the study did not evaluate cognitive changes. When administered to 1-month-old mice, the protein reductions lasted through 12 months of age. “The effect lasted over 11 months following a single administration,” Perez-Pinera said. “Since changes in DNA are expected to be permanent, we do not anticipate that further fluctuations would occur at later time points.” In safety checks, researchers found no significant unintended edits at tested DNA sites and saw no elevated markers of brain inflammation or cellular stress. However, Perez-Pinera noted the team did not search for previously unknown off-target edits beyond predicted locations. The approach remains in the early preclinical phase, with human clinical trials still years away. Before human testing can begin, researchers must refine delivery methods, run trials in larger animal models, complete safety testing, establish manufacturing standards and secure federal regulatory approval. Major hurdles remain, including spreading the treatment evenly through the much larger human brain, overcoming potential immune system rejections to the viral delivery truck, and developing single-truck editors to boost efficiency. The team is also exploring non-invasive delivery methods that would eliminate the need for brain surgery.