BOSTON – Geneticist Beverly Davidson, PhD, received the 2026 Outstanding Achievement Award from the American Society of Gene and Cell Therapy (ASGCT). Davidson is currently the chief scientific strategy officer at the Children’s Hospital of Philadelphia (CHOP) and a former president of ASGCT.
Some of the research Davidson presented was conducted at a new biotech company she co-founded called Latus Bio, which earlier this month announced it had raised $97 million in a Series A round. The company develops novel AAVs to specifically target central nervous system (CNS) disorders, with a lead program in Huntington’s disease (HD).
After thanking her mentors—Bill Kelly, MD, Michael Welsh, MD, and Kathy High, MD—Davidson turned her attention to presenting new advances in engineered gene therapies. Throughout her career, she has focused on improving adeno-associated viruses (AAVs) for CNS gene therapies, with a particular emphasis now on HD. Key elements include selecting the right cargo and developing the appropriate delivery vehicle. Her goal is to scale lab research in neurons, mouse models, and non-human primates (NHPs) to treat patients, including adults with HD.
Major hurdles to tackling genetic diseases of the brain include scalability and a lack of potency, Davidson said. The search for alternative AAV serotypes to AAV2 that could target neuronal cells began back in 2000. IV administration does not provide sufficient targeting to the brain. Even AAVs that have been engineered to enter the brain from the blood have high peripheral exposure and a high cost of goods per patient, which significantly lowers scalability and impact. (In one study, liver biodistribution of AAV was many orders of magnitude higher than in the CNS.)
Davidson focused on HD, the late-onset, dominantly inherited genetic disease. The identification of the gene harboring the HD mutation in the early 1990s by a consortium of researchers was one of the biggest success stories in human genetics. Even more remarkable was the underlying disease mechanism—the expansion in exon 1 of the gene of a triplet repeat sequence (CAG) producing an abnormally long string of glutamine residues in the huntingtin protein.
The right target
One of the major challenges in devising a gene therapy for HD is ensuring that the therapeutic reaches the right network—the deep brain and cortical areas. Therapies have to reach the right circuit, and the right cells in those circuits, Davidson said. Over the years, her group has tailored AAVs for delivery to the brain, inserting peptides into exposed loops of the virion to allow for targeting and unbiased diversity for blood-to-brain delivery. Nowadays, she said, machine learning approaches can be applied for further capsid improvements.
Davidson’s CHOP lab developed a method for screening AAVs with enhanced potency for CNS therapies. After generating huge libraries containing tens of millions of novel capsids, the group performed serial enrichments to identify the most attractive capsids. After screening pools of injected capsids into two species of monkeys, a winning capsid emerged: AAV-DB-3.
Davidson’s group infused AAV-DB-3 into NHPs, looking for targeting to the putamen (base of the forebrain) and caudate regions. Those results were published in Nature Communications in 2025. “AAV-DB-3 really stood out for its ability to transduce deep layer cortical neurons that are important” in HD, Davidson said. Moreover, the results were achieved with relatively low doses and only required a single infusion per hemisphere, outperforming the widely used AAV5.
Somatic instability
With a promising delivery vehicle identified, Davidson next addressed the therapeutic strategy, which takes aim at the somatic expansion of the CAG repeat. This codon grows longer over time in certain cells in the brain, sometimes expanding to hundreds of repeats.
MSH3 is a DNA repair protein that is required for CAG repeat expansions, as seen in mouse models of HD and other triplet repeat disorders, including myotonic dystrophy. Research led by Paul Ranum, PhD, who is a co-founder of Latus Bio, posted in a preprint on bioRxiv earlier this year, modeled the impact of lowering levels of MSH3 on somatic instability.
Ranum and colleagues used an artificial microRNA showed to lower MSH3 levels in NHPs by 48-94 percent. Computational modeling suggests that this would reduce somatic instability and delay onset of HD symptoms by many years. Early studies using a well-known HD mouse model, the Q111 mouse, to assess biodistribution, quantify knockdowns, and assess the impact on somatic CAG repeat expansion. AAV-DB-3 expression is highest in the striatum and cortex at 16 weeks, dropping MSH3 levels by 50%.
Davidson closed by emphasizing the need to ensure scalability for treatment beyond ultra-rare disorders. Latus hopes to file an Investigational New Drug application for its HD therapy, LTS-201, in the second half of 2026. At least two other biotech companies are also targeting MSH3 by other means.
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