CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing technology that allows scientists to modify DNA with unprecedented precision. Discovered in the early 2010s, CRISPR technology leverages a natural defense mechanism used by bacteria to protect against viral infections. The system uses a guide RNA to direct the Cas9 enzyme to a specific location in the genome, where it creates a double-strand break. This break can then be repaired by the cells natural mechanisms, allowing for the addition, deletion, or modification of genetic material. CRISPR companies are seeing more and more success in the clinic and the market is growing.

CRISPR has rapidly become one of the most powerful tools in genetic engineering, enabling precise changes to the DNA. Its applications are not limited to medicine, which will be our focus in this article, as it also allows the creation of crops with desirable traits in agriculture for instance.

In recent years, the field of CRISPR technology has improved and different forms of the technology are now being leveraged by biotech companies. Prime editing and base editing are innovative CRISPR-related technologies aiming to improve the versatility and precision of therapies.

After CRISPR Therapeutics and Vertex Pharmaceuticals collaborative success leading to CASGEVYs approval by the U.S. Food and Drug Administration (FDA) and Editas Medicines promising efforts to treat blindness, here are eight companies keeping the CRISPR field dynamic.

Beam Therapeutics was founded in 2017, and is headquartered in Cambridge, Massachusetts. The CRISPR technology company develops precision genetic medicines using its proprietary base editing technology.

The company went public on NASDAQ in February 2020 and has raised a total of $689 million since its creation according to Crunchbase.

Beams base editing technology distinguishes itself by focusing on single-base alterations, which can correct mutations at the nucleotide level. This precision reduces the risk of off-target effects and enhances the potential for treating a wide range of genetic disorders. The companys base editing platform includes the REPAIR (adenosine to inosine) and RESCUE (cytosine to uracil) systems for RNA editing, enabling targeted genetic modifications.

Beam Therapeutics has several key candidates in various stages of development:

Eligo Bioscience is a French company founded in 2014. The company focuses on precision gene editing of the microbiome to treat diseases driven by bacterial genes. Eligo Bioscience leverages its proprietary Gene Editing of the Microbiome (GEM) platform to develop therapies that target and modify specific bacterial populations. Eligo Bioscience recently raised $30 million in a series B funding led by Sanofi Ventures.

The companys GEM platform uses engineered bacteriophages to deliver CRISPR-Cas systems directly to specific bacteria within the microbiome. This approach allows for the precise elimination of pathogenic bacteria or the correction of harmful bacterial genes without disrupting the overall balance of the microbiome. By targeting bacterial genes in vivo, Eligos technology aims to address various diseases associated with microbiome dysbiosis, including antibiotic-resistant infections and chronic diseases.

Unlike broad-spectrum antibiotics, which indiscriminately kill bacteria and disrupt the microbiome, Eligos technology selectively targets pathogenic bacteria or genes within the microbiome. This precision reduces collateral damage to beneficial bacteria which helps maintain a healthy microbiome.

In January, Xavier Duportet, chief executive officer (CEO) of the company, was our guest on the Beyond Biotech podcast to talk about its flagship product EB005 targeting acne vulgaris. This candidate is on track to reach the clinic and expand its application to oncology.

Founded in 2018 and headquartered in South San Francisco, California, Epic Bio is focused on developing therapies to modulate gene expression in vivo using its proprietary Gene Expression Modulation System (GEMS) platform. The company launched in 2022 with a $55 million series A round.

Epic Bios approach combines a miniature DNA-binding protein called CasMINI with customized guide RNAs and a wide array of modulator proteins. CasMINI, licensed from Stanford University, is the smallest Cas protein to date, less than half the size of Cas9 and Cas12a, allowing for efficient delivery using adeno-associated virus (AAV) vectors. This platform enables precise gene modulation, expanding the potential for treating a variety of genetic diseases.

The CasMINI protein is engineered to function effectively in cells and is small enough to be delivered in vivo using AAV vectors. This compact size and robust functionality make it possible to target a wide range of tissues and organs with high precision.

Epic Bios pipeline is still preclinical and targets a wide variety of diseases. The companys lead candidate targets facioscapulohumeral muscular dystrophy (FSHD), a genetic muscle disorder characterized by progressive muscle weakness and wasting. The company also develops candidates for heterozygous familial hypercholesterolemia (HeFH), a genetic disorder characterized by high cholesterol levels, and retinitis pigmentosa, a group of inherited disorders that cause progressive retinal degeneration, leading to vision loss.

Locus Biosciences is a biotechnology company founded in 2015 and headquartered in Morrisville, North Carolina. The company specializes in developing precision antibacterial therapies using CRISPR-Cas3-enhanced bacteriophage technology, known as crPhage. Locus Biosciences most recent funding is a $35 million series B round in 2022.

The company employs a CRISPR-Cas3 system for its antibacterial therapies. Unlike the more commonly used Cas9, Cas3 destroys the DNA of target bacteria irreversibly, making it highly effective against antibiotic-resistant strains. This technology is delivered using engineered bacteriophages, viruses that specifically target bacteria, allowing the preservation of the microbiome.

The CRISPR-Cas3 system sets Locus apart by offering a genetic chainsaw approach, which differs from the genetic scissors approach of CRISPR-Cas9. Cas3s ability to degrade large segments of DNA makes it particularly effective for combating multi-drug resistant bacteria.

Locus lead candidate LBP-EC01 is currently in phase 2/3 and targets Escherichia coli (E. coli) infections. E. coli is a type of bacteria commonly found in the intestines of humans and animals. While most strains are harmless and part of the normal gut flora, some can cause serious infections. E. coli infections can occur through the consumption of contaminated food or water or by contact with animals or person-to-person spread.

LBP-SA01, another candidate in the companys pipeline, targets staphylococcus aureus infections. While it often exists harmlessly, it can cause a wide range of infections if it enters the body through a cut or a wound.

Founded in 2017 and headquartered in Brisbane, California, the company leverages its proprietary CRISPR platform for therapeutics and diagnostics. Like Caribou Biosciences we mentioned last week, this CRISPR company was co-founded by Nobel laureate Jennifer Doudna.

Mammoth Biosciences has raised substantial funding, including a $150 million series D financing round in 2021, which has elevated its status to a unicorn with a valuation of over $1 billion.

Mammoth Biosciences focuses on the discovery and engineering of novel CRISPR systems, specifically the ultra-small Cas14 and Cas (phi) enzymes. These systems are smaller and have an increased temperature stability, and faster reaction, which enhance their effectiveness in in vivo genome editing and diagnostics.

The use of Cas14 and Cas enzymes allows Mammoth Biosciences to develop CRISPR-based solutions that are more efficient and versatile. The smaller size of these enzymes enables easier delivery into cells, especially for diseases that affect the central nervous system.

Mammoth Biosciences is developing both therapeutic and diagnostic products. The companys therapeutic pipeline is still in the preclinical and research stages, and the indications of its candidates are mostly undisclosed.

Additionally, Mammoth has its diagnostic platform, the DETECTR platform, which is a CRISPR-based detection system.

Prime Medicine was founded in 2019 and is headquartered in Cambridge, Massachusetts. The company focuses on developing gene editing therapies using its proprietary prime editing technology. Prime editing aims to address the root causes of genetic diseases by precisely correcting mutations at their source.

The company launched with $315 million in financing, comprising a $115 million series A round followed by a $200 million series B round.

Prime Medicine utilizes prime editing, a novel gene editing technology that acts like a DNA word processor to search and replace disease-causing genetic sequences. Unlike traditional CRISPR methods, prime editing does not create double-strand breaks in DNA, which reduces the risk of unintended modifications. This technology can correct a wide range of genetic mutations, making it an interesting and promising tool for developing therapies for genetic disorders.

The technology employs a fusion protein combining a Cas protein with a reverse transcriptase enzyme and a guide RNA (pegRNA) to direct the correction process. This approach allows for highly specific and predictable edits at the targeted genomic location, minimizing off-target effects.

Prime Medicine is advancing several preclinical programs targeting various genetic diseases: Wilsons disease, preventing the body from properly eliminating excess copper and leading to severe brain and liver issues, glycogen storage disease, and retinitis pigmentosa, among others.

Primes most advanced program, however, is an ex vivo therapy in phase 1/2 targeting chronic granulomatous disease, an inherited immunodeficiency disorder that affects the bodys ability to fight certain infections.

Scribe Therapeutics is a molecular engineering company founded in 2018 and headquartered in Alameda, California. The company focuses on developing advanced CRISPR-based genetic medicines and collaborates with industry leaders such as Biogen or Sanofi.

The company recently completed a $100 million Series B financing round led by Avoro Ventures and Avoro Capital Advisors.

Scribe Therapeutics leverages its CRISPR by design platform, which includes custom-engineered CRISPR enzymes. By optimizing the CRISPR enzymes for greater efficiency, Scribes XE technology can achieve more precise and robust gene edits.Scribes XE platform features advancements in delivery technologies, such as viral vectors and lipid nanoparticles, that are optimized for delivering CRISPR components into target cells and tissues in vivo.

The CRISPR company works on several therapeutic areas hand in hand with key players in the industry. Scribe is collaborating with Biogen to develop CRISPR-based therapies for amyotrophic lateral sclerosis (ALS). In partnership with Sanofi, Scribe is also working on genetically modifying natural killer (NK) cell therapies for cancer treatment. The XE platforms high specificity and efficacy make it ideal for engineering these cells to target and eliminate cancer cells effectively.

SNIPR Biome was founded in 2017 and is headquartered in Copenhagen, Denmark. The company specializes in developing CRISPR-based microbial gene therapies aimed at precisely targeting and eradicating pathogenic bacteria, including antibiotic-resistant strains.

SNIPR Biome has raised notable funding including one of Europes largest series A rounds, securing $50 million.

SNIPR Biomes primary technology involves CRISPR-Guided Vectors (CGV), which deliver CRISPR components into bacterial cells via engineered bacteriophages. These vectors create double-stranded breaks in the DNA of target bacteria, leading to rapid and specific bacterial killing. This approach is designed to preserve beneficial microbiota while targeting harmful pathogens, particularly those resistant to conventional antibiotics.

SNIPR001 is the companys lead candidate, a CRISPR therapy targeting E. coli, including antibiotic-resistant strains. SNIPR001 is designed to prevent bloodstream infections in patients undergoing hematopoietic stem cell transplants, who are particularly vulnerable to such infections. Positive interim results from phase 1 clinical trials showed that SNIPR001 was well-tolerated and effectively reduced gut E. coli levels in treated individuals.

The CRISPR technology market is experiencing robust growth and substantial investments. In 2024, the global market was valued at approximately $3.78 billion and is projected to reach around $9.34 billion by 2029, growing at a compound annual growth rate (CAGR) of 19.9%. This promising outlook for the CRISPR market is driven not only by the recent success of companies like Vertex and CRISPR Therapeutics but also by the emergence of more refined versions of the CRISPR technology.

While there is no doubt CRISPR has a bright future ahead, the market faces several challenges. The high costs associated with CRISPR technology are one of the main obstacles to its democratization in the future. Ethical concerns regarding genetic modifications and regulatory hurdles are also significant obstacles as ethics and law always move slower than technology.

More broadly, the gene editing and engineering scenes are moving fast, and technologies such as epigenetic editing and gene writing with companies such as Chroma Medicine and Tessera Therapeutics show significant potential.

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Seven CRISPR companies to watch in 2024 - Labiotech.eu

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