PHILADELPHIA, PA — Latus Bio, Inc. has unveiled groundbreaking research on a novel adeno-associated virus (AAV) capsid variant, AAV-Ep+, which shows significant promise for advancing gene therapy applications. Published in the journal Science Translational Medicine, the study highlights AAV-Ep+ as a potent tool for delivering therapeutic proteins across the central nervous system (CNS), addressing lysosomal storage disorders (LSDs) and potentially other neurodevelopmental and neurodegenerative diseases.
Developed under the leadership of Latus founder Beverly Davidson, PhD, the AAV-Ep+ capsid exhibits exceptional efficiency in targeting ependymal cells lining the brain’s ventricles and cerebral neurons. The capsid enables cells to serve as “protein production depots,” secreting high levels of therapeutic proteins into cerebrospinal fluid (CSF). This mechanism allows for widespread distribution of therapies via the CNS with a single delivery.
The AAV-Ep+ variant was identified through a large-scale, unbiased screening of a diverse AAV library in non-human primates (NHPs). The nominated capsid demonstrates the following key properties:
- Enhanced tropism for ventricular and cortical brain regions, transducing cells implicated in various diseases.
- Robust cross-species activity, effectively transducing human neurons derived from induced pluripotent stem cells, as well as cortical neurons in NHPs and mice.
- High efficiency in delivering encoded proteins at therapeutic levels, surpassing results achieved with natural AAV serotypes.
Preclinical testing of AAV-Ep+ involved low-dose administration of constructs expressing human tripeptidyl peptidase (hTPP1) to models of CLN2 disease, an LSD characterized by TPP1 deficiency. Results revealed therapeutic concentrations in both CSF and brain tissues, significantly exceeding those achieved with standard serotypes, achieving levels considered sufficient for clinical efficacy.
“This breakthrough in AAV capsid engineering represents a critical advancement in the field of gene therapy,” said Dr. Beverly Davidson, Chair of the Scientific Advisory Board at Latus Bio and the study’s corresponding author. “AAV-Ep+ offers a highly efficient, low-dose solution for brain-wide protein delivery, opening new possibilities for treating neurodevelopmental diseases like CLN2 disease and beyond.”
The implications of this innovation extend well beyond its initial applications, promising to transform therapeutic strategies for neurological disorders. By enabling precise and sustained protein delivery with minimal intervention, AAV-Ep+ could redefine gene therapy’s potential for countless patients in need of long-term, effective treatments.
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