Novel Highly Accurate Single Cell Genotyping Technology for use in Discovering Late Onset Disease-Specific Stem Cell Lines and Monitoring Aneuploidy in Developing Stem Cell Lines

Funding Type: 
Tools and Technologies I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

The creation, propagation, understanding and free distribution of novel human embryonic stem cell (hESC) lines are urgently needed in order to help medical researchers find treatments for many debilitating diseases. We propose to develop and implement a tool that can simultaneously determine the identity of hundreds of genes and also detect for aneuploidy at all 24 chromosomes in a single cell, something not previously possible to do simultaneously, and each with far greater accuracy than current methods. This will have wide ranging application in the field of stem cell research. We will demonstrate our technology on two applications. First, we will use it to try and understand the prevalence and characteristics of spontaneous aneuploidy (a change in the number of chromosomes), in developing stem cell lines, currently a significant problem. Second, we will use it to identify embryos harboring interesting disease genes and develop them into stem cell lines.

Aneuploidy plagues a large percentage of normal and disease hESC lines, rendering them unsuitable for clinical applications. Very little is known about aneuploidy in early stage hESC development. Our technology, which can detect aneuploidy with high accuracy from a single cell, will be used to monitor ploidy in developing stem cell lines to provide insight into this problem.

Disease stem cells are a very important tool for studying diseases because they respond to treatments more similarly to humans than do other models. Preimplantation genetic diagnosis (PGD) of embryos during in vitro fertilization (IVF) is the most effective method for derivation of disease-specific hESC lines. A major drawback of current PGD methods is their inability to detect both aneuploidy and multiple genes known to cause a disease. Since most PGD screens either for aneuploidy or for diseases that develop during early childhood, there is very little opportunity to serendipitously discover embryos predisposed to diseases that develop during adulthood. Because ours is the only method that simultaneously measures both multiple disease-linked genes and aneuploidy in a single cell isolated from an embryo during PGD, we will be uniquely positioned to routinely screen embryos during IVF for genes causing a predisposition to important diseases such as diabetes, Alzheimer’s disease, type II diabetes, and breast cancer. In collaboration with our key California IVF clinic partners we will apply our technology to screen thousands of embryos per year. With parental consent, embryos that test positive for susceptibility to diseases of interest will be used to derive two novel hESC lines that will be made available for free distribution to the research community worldwide.

If funded, our research will result in several critical contributions to the field of stem cell research, ranging from empowering scientists to answer fundamental biological questions to facilitating the development of targeted therapeutics.

Statement of Benefit to California: 

Our company is headquartered in [REDACTED]. We provide technical, high-salaried employment for dozens of California residents. With Series A venture backing from Sequoia Capital and Claremont Creek Ventures, and we have outlined an ambitious plan for growth, promising to bring even more jobs to the state. Additionally, we have close strategic partnerships with three California-based IVF clinics: [REDACTED] These IVF clinics, and their patients, will be among the first beneficiaries of our ground-breakingtechnologies. Most importantly, if this grant is funded, our company will be able to develop and validate a new technology for high accuracy genotyping of embryos. This technology will have many applications in the field of stem cell research, two of which we will demonstrate with this grant. First, in collaboration with the [REDACTED] Department of Genetics, we will help bring novel human embryonic stem cell lines to California scientists. These disease-specific lines will be a superb resource for Califonia researchers working to understand, prevent, and cure debilitating genetic diseases. Second, we will do basic research into the prevalence of aneuploidy in developing stem cell lines. These resources and knowledge will help keep California at the forefront of stem cell research worldwide, enriching our local economy and earning further prestige for nonprofit research institutions. Local drug companies will benefit from local resources in nonprofit stem cell research. Finally, California residents couldeventually benefit from advances in medicine that result from this important local biological resource.