14 Cutting-Edge Startups Focusing On RNA Research
For many years, the focus of therapeutic developments and scientific research was directed at the genome and proteins. Yet, there is a completely different level of cell regulation: the transcriptome level, presented by ribonucleic acids (RNAs).
RNA molecules are not just intermediates between DNA and proteins, in fact, they also carry out enzymatic functions, control gene expression, and perform other functions in cells.
Major breakthroughs in transcriptomics have been made since the beginning of the century: the discovery of RNA interference blew up the industry and the Nobel Prize in Physiology or Medicine 2006 was awarded jointly to Andrew Z. Fire and Craig C. Mello "for their discovery of RNA interference - gene silencing by double-stranded RNA."
RNA interference is a gene silencing mechanism promoted by small siRNA molecules that are also exploited in patisiran and inotersen – first-in-class RNA therapeutics. Both drugs target transthyretin, a protein involved in the pathogenesis of transthyretin-mediated amyloidosis, and reduce the expression of its mutant version.
Today, efforts by companies in the transcriptomics space are typically directed in one of the following ways:
- RNAs that modulate DNA,
- RNAs that target proteins,
- RNAs that encode proteins,
- modalities, like small molecules, that modulate RNA or related transciption machinery (e.g. splicing)
- delivery of RNA-based therapies
- other strategies, like non-coding RNAs
Among existing modalities – ASOs, single-stranded antisense oligonucleotides that block mRNA translation, siRNAs and microRNAs that degrade protein-encoding mRNAs, RNA aptamers that tightly bind specific spots on proteins and regulate their functioning, small molecules targeting RNAs or transcriptome-related proteins, and so on.
In addition to that, last year showed a real boom in mRNA vaccines, with coronavirus vaccines and cancer vaccines being the most prominent representatives.
While there are numerous companies developing RNA-based therapeutics and vaccines, including major corporations like Pfizer, BioNtech, Moderna, etc., below I am listing several biotech startups to keep an eye on.
Some of them are platform companies powered by artificial intelligence (AI):
Atomic AI
Atomic AI, founded in May 2021, is headquartered in the San Francisco Bay Area and is focused on leveraging a fusion of machine learning and structural biology to advance RNA drug discovery. The company has developed a proprietary platform that utilizes deep learning foundation models to explore and design RNA-targeted small molecules, RNA-based medicines, and RNA tools.
Atomic AI raised a total of $42 million in funding over two investment rounds, with the latest funding being secured on January 2023, from a Series A round. The company has attracted investments from 14 investors, with Nat Friedman and Neal Khosla being the most recent backers.
In a notable personnel update, Atomic AI announced the appointment of Dr. Manjunath "Manju" Ramarao, a veteran from Bristol Myers Squibb with over 20 years of experience in the pharmaceutical industry, as its Chief Scientific Officer, showcasing the company's commitment to advancing its RNA drug discovery platform.
HAYA Therapeutics
HAYA Therapeutics is developing precision medicines targeting the dark genome, focusing on long non-coding RNAs (lncRNAs) to reprogram disease-driving cell states.
They utilize proprietary tools to identify disease-associated tissues and cells, then apply RNA-targeting modalities like modified antisense oligonucleotides (ASOs) to inhibit specific lncRNAs.
This approach aims to modulate the epigenome and reverse disease processes. Their technology addresses rare and chronic diseases by leveraging the regulatory potential of dark genome-derived RNAs. This innovative strategy represents a next-generation therapeutic paradigm in biopharmaceuticals.
Anima Biotech
Anima Biotech focuses on designing small molecule drugs that modulate mRNA biology, a notoriously hard task. Normally, small molecules are designed to target proteins, but Anima’s drug modality is innovative by a mode of action.
Their approach involves targeting the processes that control mRNA behavior, such as its translation into proteins, potentially affecting disease progression and symptoms.
This innovative approach aims to develop therapeutic agents that can either enhance or inhibit mRNA function, leveraging their platform to visualize and manipulate mRNA dynamics within cells. The drugs are designed based on extensive imaging data and AI analysis, identifying compounds that can beneficially modify mRNA activity.
Anima Biotech is advancing mRNA biology with its innovative mRNA Lightning™ platform, which incorporates AI-driven technologies to discover and develop mRNA drugs, targets, and vaccines.
Image credit: Anima Biotech
Turn Biotechnologies
Turn Biotechnologies has developed the eTurna™ delivery platform, addressing the challenge of delivering RNA-based treatments.
This platform is customizable for different types of cargoes and routes of administration, using ionizable lipids that are safer and clear the body quickly. It reduces immunogenicity and enhances delivery efficiency.
The company focuses on delivering mRNA therapies to various cells and tissues, including skin and blood cells, with plans to expand into dermatology, immunology, ophthalmology, osteoarthritis, and muscle therapies.
What is especially interesting is Turn Bio’s focus on rejuvenation.
Recently, the company received positive feedback from the FDA during an INTERACT meeting regarding their skin rejuvenation therapy, TRN-001.
This treatment aims to rejuvenate skin cells at the cellular level, showing promise in improving skin integrity, reducing inflammation, and enabling hair follicle transfection in preclinical studies.
This positive FDA feedback positions Turn Bio to potentially be the first longevity company to take cell rejuvenation to the clinic.
Mana.bio
Mana.bio is a promising biotech startup that was established in 2021 and operates primarily out of the San Francisco Bay Area, though it also has a notable presence in Tel Aviv, Israel. The company uses artificial intelligence-based approach to improve the development of lipid nanoparticles (LNPs) for oligonucleotide therapies, which encompass DNA and RNA-based therapeutics as well as vaccines. As delivery is a crucial bottle-neck for RNA/DNA therapies in general, Mana.bio can potentially unlock new therapeutic horizons and contribut to the advancement of personalized medicine.
Financially, Mana.bio secured $19.5 million in a seed investment round from Andreessen Horowitz Bio + Health, Base4 Capital, NFX, LionBird, and Technio, underscoring a significant vote of confidence in the company's innovative approach.
Orna therapeutics
Orna therapeutics is a Cambridge-based biotech startup founded in 2019 whose main focus lies in the novel field of circular RNAs (oRNAs) which is the next step in RNA-based therapies. The company’s innovation relies on the groundbreaking results of Prof. Daniel Anderssons’s group (MIT) that investigated oRNAs and found its superiority over linear analogs in terms of stability, protein expression, and synthetic availability. The potential applications of this technology are far-reaching, including Orna’s initial focus on developing in situ CAR-T delivery system which avoids costly and complicated procedures of the current immunotherapies. The company already managed to close the Series A round in February 2021 raising $80 million from a group of prominent healthcare investors including F2 Ventures, Taiho Ventures, and MPM Capital.
In May, 2023, Orna Therapeutics disclosed advancements regarding its circular RNA platform. Specifically, ORN-101, an optimized development-stage in situ CAR program, shows tumor eradication in a mouse model at doses far lower than previously reported results. Orna's FoRCE screening platform has enabled the identification of oRNAs that drive high protein expression, creating broad value across all of Orna's programs.
Financially, Orna secured a robust position with a successful Series B financing round on August, 2022, raising a staggering $221 million. Additionally, the company has entered a partnership with Merck to discover, develop, and commercialize multiple programs, including vaccines and therapeutics in the areas of infectious disease and oncology.
Korro Bio
A US-based startup Korro Bio has a smart approach to gene editing that relies on the natural RNA editing system, already present in all human cells. The company utilizes the short synthetic RNA strands to activate the ADAR (Adenosine Deaminases Acting on RNA) and guide it to make a specific fix in the messenger RNA. In comparison to CRISP technology when DNA gene material is altered directly, RNA editing only alters the genetic messenger and could be stopped at any time in case of adverse reactions. It also eliminates the need for an intrusive injection of a third-party enzyme, therefore decreasing the risk and optimizing the safety profile.
Although the company was founded in 2020 it has already raised a Series A in Sep 2020, attracting $91.5 million with Wu Capital as the lead investor.
In a pivotal move to harness the potential of RNA editing technology, Korro Bio and Frequency Therapeutics underwent a merger in July 2023. The merged company continues under the moniker of Korro Bio.
In its pursuit of RNA-driven innovation, in March 2023 Korro Bio inked a collaboration and license agreement with Genevant Sciences, focusing on the development of lipid nanoparticles (LNP)-based RNA therapies.
Shape therapeutics
Shape therapeutics also leverages a natural ADAR RNA editing system and makes use of it in the number of their products, such as the RNA Fix™ system for single-mutation genetic diseases. They have also developed an RNA Skip™ to fix the mutations associated with premature stop codons and enable the production of fully corrected protein. In order to face the delivery challenges, they are developing an AAVid™ capsid delivery platform which through the screening between millions of possible AAV (Adeno Associated Viruses) selects the most suitable for specific disease tissues.
The company was founded in Seattle, USA in 2018 and gained attention from notable investors, including New Enterprise Associates, Tectonic Associates, Mission BioCapital who believed in the company's future and took part in Series A totaling $35.5 million.
At ASGCT 2023, the company announced seven presentations that spotlight its groundbreaking programmable medicine technology, enabled by artificial intelligence. This technology harnesses the power of AI and RNA to address genetic diseases. Shape’s CEO, Francois Vigneault, shared some notable advances in CNS in vivo at the J.P. Morgan 41st Annual Healthcare Conference. Those included highlights across the ShapeTX technology platforms, including breakthrough results from ShapeTX's AI-driven AAVid™ capsid discovery platform and TruStable™ AAV manufacturing technology platform.
Moreover, in a lucrative move, Shape Therapeutics entered into a $1.5 billion deal with Otsuka. This collaboration is designed to develop gene therapies targeting eye diseases, intertwining Shape’s AI-driven AAV platform with Otsuka’s deep-rooted expertise in ophthalmology13.
Remix Therapeutics
The majority of the diseases are caused by protein malfunction and therefore are the main targets in the current pharmaceutical world. Remix Therapeutics, a company founded by former Atlas Venture Executive in Residence Peter Smith in 2019 in Cambridge USA, decided to get back to the origin of protein expression and alter at the level when the RNA sequences are produced.
They are using small molecule therapies which have advantages of simple dosage and increased stability inside the living organism. Their research team presented a REMaster technology for the development of new therapies which consists of three main parts, such as a database of RNA messengers, screenings techniques to validate the target and a custom library of small molecules.
After an initial seed round when Atlas Ventures and The Column group supported the company with $16 million in Jan 2019, they quickly attracted more investors and held Series A raising an additional $65 million led by Foresite Capital in Dec 2020.
In February 2022, the company parntnered with industry heavyweight Johnson & Johnson. Together, they aimed to develop small-molecule therapeutics with the capability to reprogram RNA processing, targeting up to three diseases in the realms of immunology and oncology.
Financially, Remix has accumulated $151 million over three funding rounds, with the most recent Series B round concluding in May 2022 -- $70 million.
Deep Genomics
Deep Genomics utilizes its proprietary AI platform, BigRNA, to develop RNA-based therapeutics targeting genetic diseases. BigRNA is a transformer-based deep learning model trained on thousands of RNA-seq datasets, encompassing over a trillion genomic signals.
This platform can predict tissue-specific regulatory mechanisms of RNA expression and identify binding sites for RNA-binding proteins and microRNAs. It excels in analyzing the effects of non-coding, missense, and synonymous variants on gene regulation and designing therapeutic candidates such as steric blocking oligonucleotides (SBOs), which can modulate RNA splicing to treat diseases like Wilson disease and spinal muscular atrophy.
BigRNA’s advanced capabilities enable it to predict RNA expression at sub-gene resolution, which allows for precise regulatory interventions. This model has shown effectiveness in identifying pathogenic variants and understanding their molecular mechanisms, significantly outperforming other state-of-the-art technologies in predicting the binding sites of proteins and microRNAs.
Through this innovative approach, Deep Genomics is pioneering the development of precision medicines that can correct RNA splicing defects and other genetic abnormalities, aiming to transform the treatment landscape for various genetic conditions.
Radar Therapeutics
Radar Therapeutics, founded in 2023 and based in Berkeley, California, develops RNA interference (RNAi) therapies. Their platform uses RNA sensors to achieve targeted and timed delivery of therapeutic payloads, leveraging AI and single-cell transcriptomic data to identify precise cellular signatures. In May 2024, the company raised $13.4 million in seed funding led by NfX Bio, with contributions from Eli Lilly, Biovision Ventures, and others.
Strand Therapeutics
Strand Therapeutics is a biotechnology company focused on programmable mRNA therapeutics. Founded in 2017 in Cambridge, Massachusetts, by MIT researchers, Strand leverages synthetic biology to create autonomous mRNA medicines capable of sophisticated cellular targeting and control.
The company's innovative approach involves embedding logic-based circuits into mRNA, enabling precise therapeutic delivery only to diseased cells.
Strand has secured over $100 million from investors including Playground Global and FPV Ventures. In 2023, it partnered with BeiGene to develop multi-functional mRNA treatments for solid tumors.
aceRNA Technologies
aceRNA Technologies is a Japanese biotech company focused on mRNA-based therapeutics. It was founded in 2018 by Professor Hirohide Saito and is located in Kyoto. It utilizes the proprietary RNA Switch technology, which allows precise control of gene expression in specific cells, minimizing side effects and enhancing therapeutic efficacy. This innovation integrates a switch mechanism into mRNA, which can be toggled on or off depending on the presence of specific microRNAs (miRNAs) within the target cells.
In 2024, aceRNA raised 960 million JPY (approximately 6.1 million USD) in a Series B funding round from investors including DCI Partners, UTokyo Innovation Platform, Mitsubishi UFJ Capital, and Kyoto Capital Partners. Also, this year the collaboration with Pfizer was announced to advance RNA Switch technology for targeted mRNA therapies.
Eleven Therapeutics
Eleven Therapeutics is a biotech company focused on developing RNA-based therapeutics, leveraging synthetic chemistry and artificial intelligence to revolutionize mRNA therapies. Founded in 2020 by experts in computational biology and small RNA biology, the company operates out of its main locations in Cambridge, UK, and Tel Aviv, Israel. It develops the TERÅ platform that uses massively parallel combinatorial chemistry and AI to design and optimize RNA therapeutics, creating millions of uniquely barcoded RNA molecules. This approach allows a detailed study of structure-activity relationships (SAR), advancing the development of effective RNA drugs.
Eleven Therapeutics has raised $22 million in seed funding in 2022 from a diverse portfolio of investors, including governmental grants and prominent institutions. In 2023, it began a research collaboration with Novo Nordisk to discover cell-specific carriers for nucleic acid therapeutics. Eleven Therapeutics partnered with Dong-A ST, one of the leading Korean pharma companies, to develop RNA-based gene therapies this year.
