Scribe Therapeutics change the genes responsible for causing diseases

Imagine being able to change the genes responsible for causing diseases. For Scribe Therapeutics, a gene-editing company that develops genetic medicines, this is no longer a dream but a reality. Scribe Therapeutics is one of several companies approaching genetic medicines through Crispr, the now-famous “molecular scissors” employed to cut and edit DNA. But the company is taking a new approach to leveraging Crispr technology. Instead of relying on wild-type or naturally occurring Crispr molecules such as Cas9, Scribe Therapeutics have built their own, highly-specialized varieties.

Founded by Jennifer Doudna, Benjamin Oakes, Brett Staahl, and David Savage, Scribe Therapeutics is creating an advanced platform for Crispr-based genetic medicine.

Crispr is changing how we think about treating diseases,” says co-founder, President, and CEO of Scribe Therapeutics, Benjamin Oakes. “When I finished my undergraduate degree, I shadowed doctors and realized we had no way to treat the underlying causes of diseases. This changed my career path to creating Crispr-based tools that can actually treat the underlying causes.”

Scribe Therapeutics has collaborated with Biogen to create Crispr-based genetic medicines for diseases such as amyotrophic lateral sclerosis (ALS). The company is also studying how to use adeno-associated virus (AAV) vectors to deliver Crispr components to the nervous system, eyes, and muscles. AAV vectors can deliver DNA to specific target cells for therapeutic uses.

Today, Scribe Therapeutics announced a $100 million Series B funding round that will help the company grow and expand. One of the key ways it stands out from other synthetic biology and gene-editing companies is through its approach to doing science. Other companies sometimes create tools without thinking about the problems they can solve, but Scribe Therapeutics is different. Instead of building technology in need of a solution, Scribe Therapeutics finds the problem first and creates the technology to fix it.

We face challenges head-on and continue to inspire people to try the hard things. You have to encourage fearlessness in science. If your experiment failed today, it doesn’t mean you’re a failure. You have to keep trying,” says Oakes.

Scribe Therapeutics‘ “Crispr by designplatform has custom-engineered millions of novel molecules specifically designed for therapeutic uses within the human body. For example, its X-editing (XE) technology is an engineered molecule that offers greater specificity, activity, and deliverability when used therapeutically.

Source: https://www.forbes.com/

CRISPR Treatment Destroys Cancer Cells

Researchers at Tel Aviv University (TAU) have demonstrated that the CRISPR/Cas9 system is very effective in treating metastatic cancers, a significant step on the way to finding a cure for cancer. The researchers developed a novel lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. The system, called CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors that cut the cells’ DNA.

The revolutionary work was conducted in the laboratory of Prof. Dan Peer at TAU. Dr. Daniel Rosenblum led the research together with Ph.D. student Anna Gutkin and colleagues.

To examine the feasibility of using the technology to treat cancer, Prof. Peer and his team chose two of the deadliest cancers: glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. Ovarian cancer is a major cause of death among women and the most lethal cancer of the female reproductive system. Most patients are diagnosed at an advanced stage of the disease when metastases have already spread throughout the body. Despite progress in recent years, only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%.

The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner,” said Prof. Peer. “Despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.

This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal,” explained Prof. Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”

The results of the groundbreaking study were published in November 2020 in Science Advances.

Source: https://english.tau.ac.il/
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 https://www.eurekalert.org/

Sharpen Molecular Scissors And Expand The Gene Editing Toolbox

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a “hit and run” approach.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.

One of the major challenges of CRISPR/Cas9 mRNA technologies is the possibility of off-targets which may cause tumors or mutations,” said Baisong Lu, Ph.D, assistant professor of regenerative medicine at WFIRM and one of the lead authors of the paper. Although other types of lentivirus-like bionanoparticles (LVLPs) have been described for delivering proteins or mRNAs, Lu said, “the LVLP we developed has unique features which will make it a useful tool in the expanding genome editing toolbox.

To address the inaccuracy issue, WFIRM researchers asked the question: Is there a way to efficiently deliver Cas9 activity but achieve transient expression of genome editing proteins? They tested various strategies and then took the best properties of two widely used delivery vehicles – lentivirus vector and nanoparticles – and combined them, creating a system that efficiently packages Cas9 mRNA into LVLPs, enabling transient expression and highly efficient editing.

Lentiviral vector is a widely used gene delivery vehicle in research labs and is already widely used for delivering the CRISPR/Cas9 mRNA technology for efficient genome editing. Nanoparticles are also being used but they are not as efficient in delivery of CRISPR/Cas9.

By combining the transient expression feature of nanoparticle-delivery strategies while retaining the transduction efficiency of lentiviral vectors, we have created a system that may be used for packaging various editor protein mRNA for genome editing in a ‘hit and run’ manner,” said Anthony Atala, M.D., director of WFIRM and co-lead author of the paper. “This system will not only improve safety but also avoid possible immune response to the editor proteins, which could improve in vivo gene editing efficiency which will be useful in research and clinical applications.

The WFIRM team published its findings in a paper published recently in the journal  Nucleic Acids Research.

Source: https://school.wakehealth.edu/