Cells have the same DNA, but the body has an inherent way to influence what any given cell becomes, whether it is a liver cell or a neuron. Catherine Stehman-Breen, CEO of biotechnology startup Chroma Medicine, explained that this system called epigenome takes the content of DNA and understands it. She said that if you think of DNA as hardware, then the epigenome is the software that tells the hardware what to do.
Genetic drug research is advancing therapies to treat diseases by cutting and editing the genome or by introducing genetic material designed to repair the wrong genetic code. But Stehman-Breen said that the use of epigenome provides another way and has potential advantages. Chroma is not trying to correct the mutated gene, but to control its software to regulate its expression.
“Using this mechanism gives us a huge breadth of therapeutic applications,” Stehman-Breen said. “We think it is ultimately a very powerful tool.”
Headquartered in Cambridge, Massachusetts, Chroma is building an epigenetic drug pipeline that can turn genes on or off. The startup owns $125 million raised To support its research. The Series A financing announced on Wednesday was led by Cormorant Asset Management.
Vic Myer, Chroma’s president and chief scientific officer, said that Chroma’s approach mimics what the body is already doing. Some genes, such as retroviruses in the genome, remain dormant for life because the epigenome shuts them down. Similarly, Chroma drugs silence toxic or mutated genes, allowing healthy genes to work. For haploid insufficiency, that is, a disease in which a gene in a gene pair is not functioning properly, Chroma will take the opposite approach and turn on gene expression.
Myer said that these drugs themselves are modified macromolecules that can reach specific locations in the genome. The goal is to make these therapies a one-time treatment. After the drug takes effect, when the cell divides, the epigenome system understands that specific genes should be turned off. Subsequent daughter cells remain gene silent. Myer, a former executive at Editas Medicine, a gene-editing biotechnology company, said he left the company after trying to do something different in the past five years. Chroma’s technology persuaded him to return to genomic medicine.
“This is an elegant method, a natural and normal way to turn off genes. If you want to turn off a gene, if you want to turn on a gene, turn on a gene,” Myer said.
Chroma is based on the research of its six scientific founders: Luke Gilbert, Keith Joung, David Liu, Angelo Lombardo, Luigi Nadine, and Jonathan Weissman. According to Stehman-Breen, Chroma is based on research by Weissman, Gilbert, and others. Publish In the 2016 issue of Cell, it was shown how the “CRISPRoff” fusion protein shuts down gene expression. This change is maintained as cells divide and stem cells differentiate into neurons.
Chroma, founded last year, recently acquired Epsilen Bio, headquartered in Milan, Italy. Its co-founders include Lombardo and Naldini. Stehman-Breen said that the founders of Chroma knew Lombardo and Naldini, and the ongoing dialogue led the founders to conclude that the two companies are complementary and it makes sense to develop epigenetic drugs together.
Gene silencing is the most advanced part of the Chroma technology platform. Myer said this is because silence is absolute-when you reject a gene, it is difficult to reject it halfway through. Open genes can have different gene expression set points. Myer said that from a therapeutic point of view, Chroma’s research on turning on genes is “a bit far away.”
The idea of silencing genes is probably the most well-known method of RNA interference (RNAi). These nucleic acid therapies activate an existing mechanism in the cell that prevents genes from producing disease-causing proteins. Alnylam Pharmaceuticals’ RNAi therapy received FDA approval for the first time. However, the therapeutic effects of RNAi will not last, so these treatments must be taken for a long time.
There are other ways to regulate gene expression. Constellation Pharma’s clinical-stage epigenetic drugs are small molecules that target enzymes that activate or inactivate disease-causing genes.The biotechnology that focuses on cancer research is It was acquired by MorphoSys for US$1.7 billion earlier this year. CAMP4 Therapeutics is developing programmable RNA therapy, which aims to up-regulate gene expression to solve the haploid deficiency.Cambridge CAMP4 raised $45 million in June.
Omega Therapeutics, a pioneering flagship biotechnology company Listed in July Initial public offering of US$126 million, And it is developing a therapy called “epigenome controller”. These fusion proteins are designed to target insulating genomic domains on DNA. But this Cambridge company is not a binary method of turning genes on or off, but more precisely “adjusting” the treatment to the correct gene expression level and the correct duration. Omega’s main therapeutic drug candidate modulates a gene that is difficult to target, and its activity is related to the progression of a variety of cancers. Turning down rather than turning off genes is the best way, because healthy cells also rely on genes. CEO Mahesh Karande explained to MedCity News earlier this year.
Chroma has not disclosed the diseases it aims to treat. Stehman-Breen said that the $125 million is the total amount of funds raised by the company since its inception. She estimates that as the startup continues to build a technology platform and develop new therapies, the cash will last for two years.
Other investors in the financing include Casdin Capital, Janus Henderson Investors, Omega Funds, funds and accounts advised by T. Rowe Price Associates and Wellington Management, as well as seed investors Atlas Venture, Newpath Partners and Sofinnova Partners.
Photos of Flickr users Dean Hawkman Through knowledge sharing license
