• Validating AAV Efficacy in Complex Neurometabolic Disease Models.*

How do you model the progressive neuropathology of LSDs in preclinical efficacy studies?

A: We utilize established and validated in vivo models that recapitulate key aspects of human lysosomal storage disorder pathology, including substrate accumulation, lysosomal dysfunction, and progressive neurodegeneration. Model selection is aligned with the specific LSD and the AAV therapy’s mechanism of action to ensure clinical relevance.

What are the primary efficacy endpoints for AAV gene therapies targeting CNS-manifesting LSDs?

A: Primary endpoints are multifaceted. They include biochemical correction (e.g., reduction of stored glycosaminoglycans), restoration of target enzyme activity in brain and CSF, and functional neurological outcomes assessed through a battery of neurobehavioral tests. Histology and biomarker analyses provide mechanistic confirmation.

How is vector biodistribution correlated with functional outcomes in these models?

A: We quantify vector copy number (VCN) and transgene expression across multiple CNS and peripheral tissues using ddPCR and RT-qPCR. These molecular data are correlated with functional readouts and histology findings to establish a clear relationship between vector delivery, protein expression, and therapeutic effect.

What strategies mitigate immunogenicity in long-term efficacy studies?

A: Mitigating immune responses to the AAV capsid or transgene product is managed through careful study design, including the potential use of transient immunosuppressive regimens. Our approach is informed by deep expertise in vector biology and immunology to interpret findings and their implications for a successful 18-24 month IND timeline.

Demonstrating durable efficacy for AAV-based gene therapies targeting lysosomal storage disorders (LSDs) requires specialized in vivo models that accurately reflect human disease. The primary scientific challenge is achieving widespread and sustained transgene expression within the central nervous system to correct underlying pathology and reverse functional deficits. Franklin Biolabs provides comprehensive preclinical programs that integrate advanced neurobehavioral assessments with robust bioanalytical and histology endpoints to validate therapeutic efficacy and de-risk clinical translation.

Optimizing Vector Specificity and Safety

For AAV therapies, particularly those employing gene editing payloads, ensuring target specificity is a primary objective. Research into vector design has shown that strategies such as self-targeting and the use of short promoters can significantly reduce nuclease expression, thereby minimizing off-target activity (PMID: 33359790). Incorporating these advanced vector designs into preclinical programs provides a clearer assessment of the therapeutic window and reduces the risk of unintended genetic modifications. This focus on precision is a key component of building a robust safety profile for regulatory submission.

As an organization launched in 2024, our continuity of service is built upon the deep expertise of our scientific team, whose legacy of collaboration has transitioned seamlessly to Franklin Biolabs.

“We started collaborating with UPenn Vector core in 2023 and the AAV vector which they manufactured laid a foundation for development of a gene therapy candidate which will enter soon preclinical studies. The key people from UPenn Vector Core joined Franklin Biolabs and our partnership transitioned without interruption… Franklin Biolabs is our trusted partner in our AAV-vector based gene therapy candidate development and we hope to continue the partnership for years to come.”
— Biotech Partner

Our integrated approach combines these advanced vector strategies with comprehensive non-target tissue biodistribution and toxicology studies under a unified GxP framework. This provides the high-resolution pharmacology validating complex biologicals required for a confident IND filing.