Latus Bio, Inc. (Latus), a biotechnology company pioneering advances in AAV gene therapy, has announced new research published today in Science Translational Medicine, “AAVs engineered for robust brain transduction drive therapeutically relevant expression of secreted recombinant protein in NHPs and a mouse model of lysosomal storage disease.”
The study, led by Latus founder Beverly Davidson, PhD details the development of a novel adeno-associated virus (AAV) capsid variant - AAV-Ep+ - that demonstrates unprecedented potency in transducing cells that line the ventricles, known as ependymal cells, and cerebral neurons in mice and in non-human primates (NHPs). This advancement is potentially a significant leap forward for therapeutic gene delivery, wherein the study authors demonstrate that cells transduced with AAV-Ep+ can effectively serve as protein production depots, secreting large amounts of soluble proteins into the cerebral spinal fluid (CSF) for uptake throughout the central nervous system (CNS). This potency and distribution profile could potentially result in one-time delivery of gene therapies that encode protein treatments for lysosomal storage disorders (LSDs) as well as for other neurodevelopmental and neurodegenerative diseases that result in long term benefits for patients.
The AAV-Ep+ 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:
- Remarkable tropism for cells that line the ventricular system of the brain and spinal cord of adult NHPs and mice. It also efficiently transduces neurons in cortical regions of the brain that are implicated in many diseases.
- Robust transduction of induced pluripotent stem cell (iPSC)-derived human neurons and mice when compared to naturally occurring AAV serotypes. This cross-species activity highlights the potential for AAV-Ep+ to deliver sustained and therapeutic expression of encoded proteins in human brain cells that could result in prolonged therapeutic benefit for patients.
Low dose administration of AAV-Ep+ constructs designed to express human tripeptidyl peptidase (hTPP1) to mice deficient in TPP1 (a model of human CLN2 disease - a type of LSD) as well as to NHPs result in CSF and parenchymal tissue levels that exceeded those obtained with natural serotype capsids, reaching levels that are potentially multi-fold above therapeutic values required for CLN2 patients.
"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 of Latus Bio and corresponding author of the study. "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 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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"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 of Latus Bio and corresponding author of the study.