SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–#biotech—Gordian Biotechnology, a biotechnology company focused on discovering and validating therapeutic targets through causal biology, today announced the release of a new preprint, titled: “A Multispecies, Modality-Agnostic Scalable In Vivo Mosaic Screening Platform for Therapeutic Target Discovery,” which describes a scalable in vivo perturb-seq platform that enables pooled genetic screening directly in living organisms across multiple tissues and disease contexts.
Over the past decade, human genetic studies and single-cell atlases across human and animal tissues have revealed an abundance of disease-associated genes. However, these approaches are fundamentally correlative: they show what genetic targets are linked to disease, but not whether altering a specific gene will meaningfully change disease progression. This gap between correlation and causation remains a major bottleneck to successful drug discovery.
Pooled perturbation screens combined with single-cell sequencing, known as perturb-seq, were developed to address this challenge, but their application has largely been confined to in vitro systems or narrowly scoped in vivo models.
In the newly released preprint, Gordian describes a platform that extends large-scale pooled in vivo screening across multiple species and tissue contexts. A computational framework for predicting physiological endpoints from transcriptomic cell states allows ranking and prioritization of therapeutic potential for large pools of gene targets, on the basis of paired transcriptomic-and-physiological datasets from human patients. This extends the utility of pooled perturbation screens directly in living organisms beyond open-ended biological discovery, to support target prioritization in drug discovery with causal testing in intact tissue microenvironments.
A key supporting innovation described in the work is the use of pooled and barcoded viral serotype screening to deliver perturbations to specific tissues in vivo. This enables systematic interrogation of gene function across biologically relevant disease contexts, including fibrotic models, while maintaining the scale required for high-throughput discovery.
Importantly, the platform is designed to evaluate targets relevant to essentially all major therapeutic modalities, including small molecules, antibodies, recombinant proteins, and gene therapies. By linking in vivo genetic perturbations to single-cell transcriptional outcomes, the approach enables direct comparison of target effects across tissues and modalities.
“The industry has identified hundreds of genes that correlate with any given chronic condition, but only a few percent of these have been interrogated for causal connection to those diseases,” said Francisco LePort, Ph.D., CEO & Co-Founder, Gordian Biotechnology. “By moving pooled perturbation screening into living systems at scale, we interrogate every single plausibly relevant gene in vivo in one experiment, rapidly identifying and validating those targets that causally drive disease biology in the contexts that matter most.”
The preprint demonstrates the ability to distinguish genes that merely mark disease-associated cell states from those that causally control them in vivo. This distinction is critical for improving translational success and reducing late-stage attrition.
“Until now, target discovery and validation has had to choose between breadth of exploration and physiological relevance of the results,” said Martin Borch Jensen, Ph.D, Co-Founder and Chief Scientific Officer, Gordian Biotechnology. “Our platform allows us to interrogate gene function directly within native tissue environments, capturing the complexity that determines whether a target will truly modify disease.”
By enabling scalable, in vivo causal screening across tissues and species, Gordian’s platform is designed to systematically improve confidence in novel therapeutic targets and eliminate false positives earlier in the discovery process. The company believes this approach addresses a foundational bottleneck at the in vivo valuation step in modern drug development.
The preprint is available on bioRxiv. Gordian currently runs pooled in vivo screening in the heart, lung, liver, joint, kidney, and adipose tissue, and is building a pipeline focused on cardio-renal-metabolic indications. The company plans to continue expanding the platform across additional tissues, disease models, and therapeutic programs.
About Gordian Bio
Gordian Biotechnology is an in vivo drug discovery company focused on curing age-related diseases. The company has built a high-throughput in vivo screening platform that tests thousands of gene targets directly in living systems to predict clinical outcomes with exceptional accuracy. The platform integrates three proprietary components: Mosaic Screening for pooled in vivo testing, Patient Avatars that closely model human biology, and Pythia, a machine-learning engine that combines screening and human data to maximize predictive power. The company is based in South San Francisco, CA. For more information, visit www.gordian.bio.
Contacts
Media Contact
Kimberly Ha
KKH Advisors
917-291-5744
[email protected]
