vivoVerse (formerly operating as Newormics) is excited to announce it has been awarded a $1.83M Phase II SBIR grant from the National Institute of Environmental Health Sciences (NIEHS) for the continued development of the company’s in vivo imaging and screening technologies.
vivoVerse’s core focus is to facilitate the use of C. elegans as a model organism for life-science research and drug and toxicology screening through its innovative microfluidics-based platform. This platform allows researchers to rapidly immobilize thousands of microscopic animals for fast and high-resolution imaging within minutes. The high-density information and an automated image acquisition approach facilitate the quantification of different phenotypes caused by chemical exposures or disease-related mutations. Using high-content C. elegans screens, vivoVerse offers in vivo developmental and reproductive toxicology (DART) and developmental neurotoxicology (DNT) testing of chemicals in a dose-dependent manner.
Product safety profiling, of which developmental and reproductive toxicology (DART) testing is an important component, is necessary to determine and continually ensure safe dosage or exposure levels of every chemical that comes into contact with humans. Toxicity testing is mostly done in genetically inbred mammals such as rats and rabbits, but public and regulatory pressure has led to directives eliminating the use of animals in safety testing where possible. vivoVerse is developing a DART assay using genetically different wild strains of a microscopic soil worm, C. elegans, to provide a faster, cheaper, and more ethical alternative to testing on mammals, and investigate population-wide differences in responses to hazardous chemicals.
Animal testing is being replaced by New Approach Methodologies in many countries
Modern toxicology assessment of chemicals is under pressure from both scientific and social sources. Traditional study models using small numbers of highly inbred mammals fail to reflect the wide genetic, geographic, and demographic variation underlying differing population-specific responses to environmental toxicants and drugs. Secondly, long-standing public pressure to reduce the use of animals in safety testing has resulted in regulatory directives to ban the use of animal studies in approvals of new chemical entities and existing chemical product re-registrations by 2035. This pressure along with continual advances in life science technology has led to the development of new approach methods (NAMs) including in vitro, ethical in vivo, and in silico methods.
Environmental justice, especially for vulnerable fence line communities at much greater risk of environmental exposure to chemicals, highlights the need to include vulnerable populations in toxicology studies. Modeling population variation in toxic responses at the necessary throughputs is not feasible using outbred in vivo mammalian models, and in vitro methods are unsuitable for assays requiring complete organisms such as developmental and reproductive toxicity (DART).
The vivoChip-24x can immobilize ~1,000 animals in 24 different populations for high-resolution phenotypic imaging
Using its novel vivoChip device, vivoVerse proposes a NAM for DART testing based on the microscopic, soil-dwelling nematode, Caenorhabditis elegans. C. elegans has a simple culturing protocol, ability to produce 300 progenies per adult, conserved toxicology pathways with humans, intact germline with tractable in utero embryogenesis, is a non-sentient invertebrate with a 3-day life cycle that is not subject to animal welfare legislation, and has well-characterized panels of several hundred naturally occurring strains with diverse genetic backgrounds, making it a highly suitable small animal model for DART assays. The vivoChip is a microfluidic-based imaging platform uniquely facilitating high-throughput toxicology assays with C. elegans, using high-resolution imaging to quantify relevant phenotypic endpoints in ~1,000 animals per chip.
In Aim 1, we will develop a new vivoChip specifically for DART testing that allows rapid immobilization of ~1,500 C. elegans of widely varying sizes. We will establish an AI/ML-assisted pipeline for automated analysis of high-resolution, on-chip images of in utero, body, and organ phenotypes relevant to DART. In Aim 2, we will develop a GLP-qualified DART assay that surveys 12 genetically diverse strains and demonstrate strain and age-specific sensitivity for two reference chemicals. In Aim 3, we will compare DART assessments with our panel of 12 strains and two sensitized mutants, with published data for chemicals of significance to stakeholders, to demonstrate the value of our assay. With a more sensitive DART assay using high-content readouts of in utero effects from twelve genetically diverse backgrounds, we expect to improve the known safety prediction accuracies of C. elegans when compared to higher mammalian models. Armed with such data, we will present our case study to the regulatory agencies for formal risk analysis, and in due course, full acceptance of C. elegans as an alternative animal model for DART, making an impact on many industries.
C. elegans is found in a variety of ecological niches around the globe, shaping its genetic makeup
vivoVerse’s in vivo toxicity services using the vivoChip® screening platform and C. elegans models will serve various industries including pharmaceutical, petrochemical, agricultural, cosmetics, and household consumer products. High-throughput toxicology screening services for new chemicals will be offered to commercial clients to identify any potential toxicity issues and accelerate the pathway to market for new products.
