PHILADELPHIA–(BUSINESS WIRE)–#GeneticPayloads—Latus Bio, Inc. (Latus), a biotechnology company pioneering advances in tissue-targeted AAV gene therapy, today announces the publication of a seminal research manuscript in Nature Communications: “Optimized AAV capsids for basal ganglia diseases show robust potency and distribution.”
The study, led by Latus founder Beverly Davidson, Ph.D., details the discovery of a novel adeno-associated virus (AAV) capsid variant – AAV-DB-3 – that is poised to address the long-standing challenge of efficient delivery to deep brain structures. Deployed via direct administration in mice and in non-human primates (NHPs), researchers identified AAV-DB-3 as the most promising candidate for targeted and robust transduction of key brain regions impacted by neurodegenerative diseases, prospectively enabling more effective gene therapies for Huntington’s disease (HD) and for Parkinson’s disease (PD) patients.
The AAV-DB-3 capsid variant was identified through a massively parallelled and unbiased screen of a large-diversity AAV variant library administered to NHPs. The nominated capsid, which was isolated from tens of millions of potential candidates, displays:
- Targeting of Medium Spiny Neurons of the Striatum and Projection Neurons of the Cortex: At dose equivalents that are 10 to 100 times lower than currently employed in the clinic, AAV-DB-3 consistently provides gene transfer to a high percentage of neurons throughout the deep brain and associated cortical regions in adult NHPs. These regions are the same as those impacted by HD and PD in humans.
- Transgene Expression: Wild-type (wt)AAV5 is currently the leading vector deployed clinically in investigational gene therapies for HD. Following direct delivery, AAV-DB-3 drives >180-fold higher transgene mRNA expression levels in HD-relevant regions of the brain when compared to wtAAV5 that administered at identical doses, volumes, and routes to analogous (contralateral) locations in the same adult NHP test subjects.
- Tropism for Human Neurons: In cultured neurons derived from human patients, AAV-DB-3 achieves >60-fold higher transgene mRNA expression levels than wild-type AAV1 at equivalent doses, indicating potential enhancements in neuronal transduction that may facilitate clinical translation.
“AAV-DB-3 represents a major step forward in solving one of the biggest challenges in both Huntington’s and Parkinson’s disease gene therapy — delivering genetic payloads precisely and effectively to deep brain structures,” said Dr. Jang-Ho Cha, Chief Scientific Officer at Latus. “These findings suggest that AAV-DB-3 and other capsid variants from our screening platform are highly promising vectors for a broad range of neurodegenerative disorders that affect deep brain and associated cortical brain regions,” said Dr. Beverly Davidson, Chair of the Scientific Advisory Board at Latus.
The study showcases Latus’ unique capsid discovery platform and ability to identify AAV capsid variants that are optimized for delivery to specific tissues and cell types, seeking to address translational shortcomings to prospectively enable better gene therapies. Latus continues to advance its pipeline of novel AAV capsid variants that target disease-relevant cell types in other regions of the central nervous system (e.g., cortex, cerebellum, spinal cord) as well as in peripheral tissues (e.g., ear, eye, heart, kidney and muscle). The Company is developing cutting-edge gene therapies that aim to transform the treatment landscape of genetically defined diseases, including many with high unmet medical needs.
About Latus Bio (Latus)
Latus is a biotechnology company dedicated to addressing devastating CNS and peripheral diseases via gene therapy. The Company is advancing an innovative therapeutics pipeline based on novel AAV capsid variants with potency and specificity. Latus is powered by a diverse team of visionary scientists, experienced clinicians, and leading industry executives. The Company has offices in Philadelphia, PA and in the Seaport in Boston, MA.
For more information, visit www.latusbio.com and follow on LinkedIn.
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