There is an intense need for more accurate screening methods during preclinical studies using in vitro assays that more closely mimic in vivo conditions. Currently, only 12% of drugs that begin phase 1 clinical trials move on to eventually receive FDA approval. One of the major reasons for this low success rate stems from inadequate preclinical testing methods. Major challenges exist in compound screening by virtue of the limited techniques using cell lines, such as Caco-2 cells (cancer cell lines), or animal studies. The physiology of these two screening methods cannot accurately predict how a compound will behave in the human body. Current in vitro models fail in at least one of three ways:
1) Lack reproducibility
2) Are low throughput
3) Do not use normal human tissue
RepliGut® tissue constructs have the potential to address critical needs in pharmaceutical drug development. Based on human intestinal stem cells, RepliGut® eliminates the issues associated with the use of immortalized cells lines, such as Caco-2. The polarized monolayers express tight junction proteins and recapitulate the barrier function of the intestine in vivo. Additionally, RepliGut® monolayers express all of the major cell lineages found in the intestinal epithelium. Because RepliGut® uses healthy, normal (not cancerous) human primary cells, they provide more physiologically relevant results. Intestinal stem cells used for the RepliGut® system are harvested from transplant-grade human donor tissue for which there is no recipient match. As such, the stem cells are very high-quality with extremely low necrotic or ischemic damage.
The form factor for the platform is an SBS format multiwell plate with Transwell inserts, and the platform can be used in 12 or 96-well plate formats, so it is high-throughput and easily integrated into standard laboratory equipment and workflows. Luminal and basal reservoirs allow compounds and additional cell types to interact with the epithelial cells for side-specific assays.
With this design, RepliGut® can more accurately model different behaviors in the intestine, such as the barrier function. Altis’ goal is to reduce the time and cost of drug development, as well as reduce the need for animal testing.
To introduce this patented, cutting-edge technology Altis will offer one company/researcher a research project (value up to $10k).
If the submitted project cost is over $10k a credit will be applied to a comprehensive program.
Types of Programs
Drug Discovery, Safety, Immunology, and Inflammation.
Permeability Assays, Transepithelial electrical resistance, Gene Expression, Protein Expression, High Content imaging, Immunohistochemistry
RepliGut® is a unique, human stem cell-derived platform that recreates the intestinal epithelium in a continuous monolayer of stem and differentiated cells. RepliGut® can be purchased as a product, or Altis Biosystems can provide the services you require.
The high throughput platform supports quick screening of many candidates and fosters efficient development through reduced timelines and costs. Focus applications include preclinical studies for compound screening, investigating the effects of diseases, and microbiome research.
- Inflammatory Bowel
- Cystic Fibrosis
- Opening Date: September 13, 2021
- Submission Due Date: November 15, 2021
- Review Dates: November 16-December 10, 2021
- Project Start Date: January 15, 2022
About the Sponsor
Altis Biosystems is a biotechnology company that has developed a patented stem cell platform which recreates the human intestinal epithelium in a high-throughput format for drug screening and microbiome research. Stem cells are sourced from transplant-grade donor intestine. Altis provides a variety of contract research services for customers and sells the platform as a kit. Services include Inflammation, Barrier Function, Toxicology, and Drug Disposition. Our goal is to reduce the time and cost of drug development with a platform that more accurately reflects native human biology and reduce the need for animal testing.
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