• Quantifying Vector Fate for Safer Clinical Translation*

Characterizing the biodistribution and shedding profile of a novel AAV capsid is a mandatory step in any IND-enabling program. These studies define the in vivo fate of the vector, quantifying its presence in target and non-target tissues and its clearance from the body. Franklin Biolabs executes these GxP-compliant studies using validated qPCR and ddPCR methodologies to generate the precise, reliable data required for regulatory submissions, directly supporting an 18-24 month timeline to IND filing.

The development of novel AAV capsids, such as Anc80 and its derivatives, aims to enhance tissue-specific tropism and improve transduction efficiency. A successful capsid engineering effort must be paired with a rigorous in vivo evaluation of where the vector distributes after administration and how it is cleared. This biodistribution profile is fundamental to the vector’s safety assessment, informing potential toxicities and the risk of germline transmission.

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Understanding non-target tissue biodistribution is a primary objective. Even with administration routes designed for local delivery, systemic exposure is a significant variable. For instance, studies have demonstrated that a high percentage of an AAV dose administered to the central nervous system can still distribute systemically (PMID: 37624734). This finding has direct strategic implications for clinical development, influencing dose selection to mitigate systemic toxicity and manage the potential for a host immune response against the capsid. Accurately quantifying vector DNA copies in all relevant tissues is a required component of the preclinical data package.

A robust study design is the foundation for generating meaningful biodistribution and shedding data. Our scientific team collaborates with sponsors to develop protocols that address the specific properties of their vector and its intended clinical application.

• Model Selection: Appropriate rodent models are selected to align with the therapeutic indication and vector tropism.

• Time Course: Multiple time points are established to map the kinetics of distribution, persistence, and clearance.

• Comprehensive Bioanalysis: A full panel of tissues and fluids is collected to build a complete picture of vector fate.

Our >100,000 sq ft facility is fully equipped to manage these complex in vivo studies, from initial dosing through final bioanalytical reporting. This integrated capability ensures data integrity and program continuity.

“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 from UPenn Vecor Core to Franklin Biolabs Research Vector Division. 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

The data from these studies form a core part of the CMC and safety sections of an IND application. Franklin Biolabs, which launched as a new brand in 2024, builds upon a legacy of work that has contributed to a 100% IND success rate for client programs since 2019. We utilize validated qPCR and ddPCR assays to provide precise quantification of vector DNA across diverse biological matrices.

All in vivo studies are conducted in strict compliance with AAALAC and USDA guidelines. We are committed to the principles of the 3Rs (Replacement, Reduction, and Refinement), ensuring the highest standards of ethical and humane animal care in our research programs.