InVivo Biosystems is the receipient of a new NIH Phase 1 SBIR award. The grant uses the model of C. elegans to address critical needs in precision medicine research.
The grant, titled “Functional Assessment of Variants in Organisms of Research (FAVOR) - Profiling Canonical Human Genes and their Variants through Disease Model Phenotyping” in the amount of $350,000 is awared by the Nation Human Genome Research Institute (NHGRI).
Precision medicine holds great promise for better patient outcomes through a deeper understanding of genetic variation. In this project, we propose to create technology that can assist in the identification of pathogenic genetic variants in humans by accurately modeling the same variants in a research animal. Ultimately, these animals can act as an avatar for patient populations bearing the same genetic variant in determining a personalized course of treatment for disease.
The expense and long timelines of mouse model production make the use of alternative small animal models attractive. In this proposal, the C. elegans nematode is used as an alternative model capable of fast high-throughput production and screening. Human genes are installed as gene-swap replacements of the native disease-gene homologs.
In this proposal, significant and novel improvements are made to our existing pipeline for the functional analysis of variants in vivo.
- In Aim 1, the relevance and extensibility of the C. elegans model system for studying human disease is improved through simultaneous humanization of multiple related loci.
- In Aim 2, new methods are developed for molecular phenotyping, improving the resolution of inputs pathogenicity determination algorithms, and yielding mechanism-of-action level readouts to variant manipulations.
- In Aim 3, the improvements to the pipeline are tested to quantify gains in pathogenicity determination on a test set of variants.
InVivo Biosystems (formerly NemaMetrix Inc.) has previously created a transgenic gene-swap humanization of STXBP1 in the unc-18 locus. This humanization rescued severe locomotion and behavior defects present in the gene knock-out animals. Pathogenic variants into the STXBP1 gene-swap loci leads to significant disruption of activity.
InVivo Biosystems is very excited to have the support of NIH in extending our capabilities. This funding will allow the company to develop more tools to address human diseases with a genetic component.