• Quantifying Nuclease Precision from Target Engagement to Phenotypic Outcome.*

How do you differentiate on-target cleavage from off-target events in vivo?

We employ a multi-faceted approach combining molecular and functional data. Tissue samples from treated subjects undergo deep sequencing using unbiased, sensitive methods like GUIDE-seq or CIRCLE-seq to identify and quantify potential off-target editing sites. This molecular data is correlated with comprehensive Histology and clinical pathology assessments of non-target tissues to determine if any identified off-target events have functional consequences.

What is the typical study duration for assessing long-term ZFN efficacy?

Study duration is tailored to the therapeutic hypothesis and target biology. For therapies intended to produce a permanent effect, such as durable protein knockdown, long-term observation periods are necessary. These studies often extend for many months to confirm the stability of the edit and the persistence of the therapeutic effect, directly informing the data package for an 18-24 month IND timeline.

How do you correlate nuclease activity with the desired therapeutic phenotype?

We integrate three distinct data streams. First, we quantify molecular engagement by measuring indel frequency at the target locus. Second, we measure functional protein knockdown or modification via ligand binding assays or other quantitative methods. Third, we assess the downstream physiological impact through relevant biomarker analysis and functional assays. This provides a complete picture from genomic event to therapeutic outcome.

Successful clinical translation of Zinc Finger Nuclease (ZFN) therapies requires a pharmacology data package that definitively demonstrates two things: potent, durable on-target efficacy and a rigorously defined safety profile. Franklin Biolabs designs and executes in vivo pharmacology studies that integrate molecular endpoints with functional outcomes. We provide the high-resolution data needed to quantify on-target activity, identify potential off-target liabilities, and build a robust, IND-ready dataset.

Animal Welfare and GxP-Compliant Execution

Our pharmacology and efficacy studies are performed within our >100,000 sq ft GxP-compliant facility, ensuring data integrity and regulatory alignment for your IND submission. By integrating molecular biology, bioanalysis, and Histology under one operational roof, we provide a cohesive data package that connects every aspect of your ZFN therapeutic’s in vivo performance.