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SAINT LOUIS, MO, United States

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 161.50K | Year: 2014

DESCRIPTION (provided by applicant): Modified ribonucleic acids (RNA) are important regulators of translation and other cellular pathways. Non- coding RNAs like microRNAs play significant roles in neuronal development, and can serve as biomarkers for psychiatric disorders. Another such modified RNA is circular RNA (circRNA), a non-coding transcript present in the cytoplasm. Since circRNAs are present in lower abundance than other RNA molecules, and share sequence homology with mRNA, they are difficult to isolate from total RNA. To facilitate identification and examination of these molecules, we propose to develop a streamlined approach that uses selective reduction of linear and ribosomal RNAs combined with a novel reverse transcriptase to enrich for circular RNAs. To optimize for robust reduction and amplification, we will test a range of conditions and assess their relative efficiencies using qRT-PCR specific for known circRNAs and synthetic spiked-in linear RNAs. We will use our validated approach to

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 918.67K | Year: 2015

DESCRIPTION provided by applicant Long term objectives Modified ribonucleic acids RNA are important regulators of numerous cellular processes and are increasingly being associated with human diseases For example non coding microRNAs play significant roles in neuronal development and can serve as biomarkers for psychiatric disorders Another such modified RNA is circular RNA circRNA a non coding transcript present in the cytoplasm Since circRNAs are present in lower abundance than other RNA molecules and share sequence homology with mRNA they are difficult to isolate from total RNA Our long term objective is to further develop and distribute a molecular biology kit which will foster broader research in this nascent field and expand our understanding of the role of circular RNAs in neuronal development substance abuse and psychiatric disorders We have established four Phase II Aims Method optimization Clinical Sample Applicability Optimization Internal Kit Testing Cofactor circRNA Service and External Field Testing Kit Beta Testers Research Design Aim We will utilize universal human brain reference RNA containing a known quantity of circRNA control and our optimized enzyme mix to determine ideal reaction parameters i e primer design temperature and incubation time that will lead to the most robust enrichment of ciRNA species Input titrations will determine the threshold and range of total RNA input for the optimized protocol Success will be measured by qPCR and sequencing metrics on libraries passing our quality control measures Aim We will obtain commercially available biobank samples such as FFPE tissue frozen brain and plasma to test the kit applicability and robustness on clinically relevant samples Quality metrics assayed by Qubit Bioanalyzer Tapestation and Nanodrop will be recorded for the corresponding sequencing libraries to identify kit robustness In addition samples provided by commercial and academic partners will further bolster our metric reports for varying sample types and input amounts Aim Our production scientists will translate the Randamp D SOP into a production service offering with client submitted samples We will continue to collect quality metrics on these samples in the production setting to determine expected yields for library construction and circRNA control enrichment We will use the data generated from both our Randamp D and production setting to develop and optimize our analysis software ActiveSite to incorporate circRNA enrichment reports Aim We have interested commercial and academic partners that have volunteered to test our circRNA kit in their respective laboratories Our partners will collect quality metric scoes about the samples generate circRNA enriched samples and provide these to us for evaluation and sequencing We will utilize feedback from these Beta testers to refine the SOP and our market strategy PUBLIC HEALTH RELEVANCE Circular RNAs are a recently discovered non canonical form of RNA that have been shown to interact with microRNAs molecules which are important in multiple neurological disorders We are developing a user friendly kit that will enable a broad range of biomedical researchers to access and study these important molecules in order to further our understanding of their role in biology and human health

As part of Y Combinator’s push into computational biology and bioinformatics, the early-stage firm is backing a team that used to work on the Human Genome Project and is now experimenting with RNA testing through a startup called Cofactor Genomics. They argue RNA, which is the intermediate step between a person’s DNA and the proteins their bodies make, is a much more accurate and real-time way of diagnosing disease. DNA, on the other hand, is predictive. It can tell you your risks of contracting a disease later in life. But for many conditions, it can’t definitively tell you if you have them at the moment. RNA also dynamically changes over time in response to what you eat and what kind of environment you’re living in. “We believe that RNA is a better barometer of health. It changes dynamically and we think it’s a much more accurate and much earlier way to diagnose disease,” said Jarret Glasscock, the company’s CEO. “DNA is pre-symptomatic. But with RNA, we think we’ll be able to see a molecular signature sooner.” Since being founded six years ago, the St. Louis, Missouri-based company has signed contracts with nine of the country’s largest pharmaceutical companies. They couldn’t disclose who, however. They also have about $1.5 million in grant funding from the National Institutes of Health. They expect to work in diagnostics for cancer, heart disease and Alzheimer’s first, and their tests use blood samples. They don’t have an expected price range for their tests, but they hope to start making diagnostics available next year. Even though they’ve been around for six years, co-founders Glasscock, Dave Messina and Jon Armstrong felt that a connection to the Valley through Y Combinator would help their business, which is in the Midwest. “They don’t necessarily have the domain knowledge, but they make these connections in the Valley that for us are extremely important,” Glasscock said. While Cofactor focuses on RNA, there is a whole wave of DNA diagnostic companies that have been funded in Silicon Valley in recent years, including Color Genomics, which tests for breast cancer risk genes BRCA1 and BRCA2, and Counsyl, which does carrier screening to test whether parents might pass on single gene recessive disorders to their future children.

News Article | August 19, 2015
Site: techcrunch.com

Smart mattress covers, RNA diagnostics, and photosynthetic grow lights were among the big ideas that shone brightest on stage at Demo Day 1 for Y Combinator’s Summer 2015 batch. Fifty startups presented on the record, including a massive influx of hardware companies and biotech firms. You can read about all of them here. And learn about Y Combinator getting hardcore about hardware here. Click through to see TechCrunch’s picks for the top 9 startups from the day. To select our picks, we asked for the opinion of some of Silicon Valley’s top venture capitalists, as well as founders in this YC class. Then, fellow TechCrunchers Matthew Lynley, Kim-Mai Cutler, and I combined these suggestions with our own favorites and debated the merits of the candidates. Continue to see our selections, in no particular order.

News Article | June 18, 2014
Site: recode.net

Revive & Restore has attracted worldwide attention for its ambitious plans to use genetic engineering to bring back extinct species, including the passenger pigeon and — perhaps, someday — the Woolly Mammoth. But Executive Director Ryan Phelan provided a reminder on Tuesday that the San Francisco research organization is working to preserve endangered animals as well. Onstage at the Techonomy Bio conference at the Computer History Museum in Silicon Valley, Phelan said the group wants to help the black-footed ferret through a crowdsourced project that will kick off next month. In a follow-up interview, she said they believe it’s the first “citizen science” project designed to aid endangered animals. The species was thought to be extinct until a colony of 18 was discovered in 1981 near Meeteetse, Wyo. Captive breeding, conservation and release programs have helped bolster the animal’s numbers during the last three decades, including efforts at the Smithsonian National Zoological Park. But Phelan noted that possible signs of inbreeding have emerged, specifically fertility issues that could get progressively worse in subsequent generations. Revive & Restore, co-founded by Phelan’s husband Stewart Brand of Whole Earth Catalog fame, has been working with Cofactor Genomics to sequence the DNA of several living ferrets as well as older specimens from the “Frozen Zoo” in San Diego (which I wrote about earlier this year). On July 15, they plan to launch a public website with clear descriptions of the challenges as well as the genomic datasets. They want to invite “citizen scientists” and professionals to help analyze the information and potentially pinpoint the genomic differences implicated in loss of fertility, low sperm count and other issues. “The idea is ultimately to help find out what areas of the genome have been compromised over time through this population bottleneck,” she said. What happens next, if anything, will be determined by the U.S. Fish and Wildlife Service, which oversees endangered animal programs. They could use the information to selectively breed those animals most likely to produce healthy offspring, perhaps through artificial insemination. “The idea would be to provide this knowledge to see if there’s anything that would help make more informed choices,” Phelan said. But long-term, whether with this species or others, there’s also the possibility of using genetic engineering to help along struggling animal populations. Researchers could potentially reproduce the healthy strands of the genome using DNA synthesis technology, splice it into stem cells and inject into a living species’ eggs — the same basic technique Revive & Restore is exploring for de-extinction. Elizabeth Kolbert, the New Yorker writer and author of the “Sixth Extinction,” said of the latter subject: “I’m pretty down on the idea. I think it’s basically being done for people, not for other species or for the planet. It’s being done because we think it’s cool or it assuages our guilt.” But the audience at the conference seemed nothing if not receptive, with one member, a science fiction writer, eagerly asking about the “ship date” for the passenger pigeon. The last one died in 1914. Phelan said they hope to produce the first birds within the next five years — and that flocks could once again fill the sky by 2025. “We don’t consider a one-off a success,” she said. “We consider the restoration of the species a success.”

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