AI Tools for Cell and Gene Therapy
AI Tools for Cell and Gene Therapy
Cell and Gene Therapies (CGT) and Artificial Intelligence
Cell therapy—also called cell transplantation, or cytotherapy—is a therapy in which viable cells are injected or implanted into a patient in order to modulate the function of the patient's cells through expression of factors or direct interaction, or the removal of disease causing dysfunctional cells using immune cells, or grafting stem cells to regenerate diseased tissues. In general, the cell therapy modality includes
stem cell- and non–stem cell-based therapies,
unicellular and multicellular therapies,
therapies with different immunophenotypic profiles. For example, immunotherapy is a form of treatment that uses the cells of our immune system to eliminate cancer cells, such as
Tumor-Infiltrating Lymphocyte (TIL) Therapy,
Engineered T Cell Receptor (TCR) Therapy,
Chimeric Antigen Receptor (CAR) T Cell Therapy,
Natural Killer (NK) Cell Therapy,
and cell therapies with different isolation techniques, mechanisms of action and regulatory levels
AI and cell therapy
🟢 Modulus Therapeutics, founded in 2020 and based in Washington, is engineering next-generation immune cell therapies starting with NK cells—natural killer cells are effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage—designed for the treatment of solid tumors. In particular, Modulus’ Convergent Design platform combines genetic engineering, ML and high-throughput in vivo screening to systematically converge on optimized cell designs to treat a broad set of patient populations not currently served by existing treatments.
At Modulus they leverage the 20+ year clinical safety record of NK cells that have a well-defined kinetic profile (unlike CAR-T, where drug kinetics can be highly variable) to express engineered receptors to overcome lymphodepletion requirement (an essential step in the application of currently used autologous and allogeneic CAR-T therapies), eliminate autoreactive cells and leverage multiple mechanisms of action to address heterogeneous diseases.
The firm was founded by Bryce Daines and Max Darnell and raised $3.5 M in seed funding in July 2021 supported by Madrona Venture Group, Allen Institute for AI and KdT Ventures.
🟢 Outpace Bio a spinout of the cell therapy company Lyell Immunopharma was founded in 2020 in Seattle by Marc Lajoie and Scott Boyken, and is pushing the boundaries of biology to create tailored cell therapy solutions through protein design and custom programming. In particular, by using Rosetta they custom design new biological functions and combine them with their cell engineering expertise trying to solve holy grail problems in cell and gene therapy.
Outpace’s OutSmart platform provides a way to regulate cytokine signaling in the tumor microenvironment—that is a major barrier to efficacy for cell therapies in solid tumors—by coordinating a productive immune response directly in the tumor microenvironment (TME) from both the engineered cell therapy as well as endogenous immune cells.
In particular, the innovative tumor-restricted IL-12 (trIL-12) technology designed leveraging the OutSmart platform delivers potent IL-12 stimulation at the tumor site while avoiding systemic exposure. IL-12 is an immune-stimulatory cytokine that can induce potent anti-tumor activity, but systemic delivery of IL-12 has been shown to cause severe toxicity in patients.
trIL-12 was designed to rapidly auto-inactivate IL-12 after inducible secretion from engineered T cells with the aim of achieving safe, local delivery of IL-12 activity, and is being advanced under a collaboration between Lyell Immunopharma and Outpace with the goal of improving efficacy for T-cell therapies while maintaining a favorable safety profile.
Outpace Bio has raised a total funding of $30M over 1 round.
🟢 Serotiny, founded in 2014 in the US by Colin Farlow and Justin Farlow, is a pre-clinical discovery company using high-throughput engineering and ML for therapeutic Multi-Domain Proteins (tMDP) such as Chimeric Antigen Receptors (CARs), CAR alternatives, accessory proteins and next generation gene editors. Serotiny has raised a total funding of $7M over 2 rounds.
So far, Serotiny had collaborations with:
Twist Biopharma, to discover novel Chimeric Antigen Receptors for CAR T-Cell therapies (a patient's T immune cells are changed in the laboratory so they will attack cancer cells) by combining Twist’s discovery platform with Serotiny’s core software engineering and high throughput assay platform and ultimately address difficult-to-treat cancers,
Tessera, to engineer programmable Gene Writer proteins that can allow the substitution, insertion or deletion of DNA sequences, as well as the writing of entire genes into the genome, and with
Janssen, to optimize CAR designs for cellular therapy, in which a patient's T cells are engineered with chimeric antigen receptors/CARs and used as a potent new class of therapeutics for cancer.
AIDPATH stands for AI powered, Decentralized Production for Advanced Therapies in the Hospital.
In the EU project AIDPATH, researchers are developing a system for the production of CAR-T cells for the treatment of cancer, integrating patient-related data and biomarkers into the therapy process using AI. The CAR-T cells are produced close to the patient, directly in the hospital.
Consortium Partners: Fraunhofer Institute for Production Technology IPT, Fraunhofer Institute for Cell Therapy and Immunology IZI, UCL, Foundation for Research & Technology - Hellas, Institute for Computer Science and Control, Universitätsklinikum Würzburg, Aglaris Cell (focused on developing novel technology for bioreactors, surface treatments and cell therapies), Fundació Clínic per a la Recerca Biomèdica, IRIS, Red Alert Labs (a cybersecurity provider helping organizations trust IoT solutions), Panaxea (a leading health research & evaluation consultancy firm), ORTEC (a provider of mathematical optimization software and advanced analytics) and Sartorius CellGenix (global supplier of high quality raw and ancillary materials for the expanding market of cell and gene therapy and regenerative medicine).
🟢 Cellino Biotech founded in 2017 by Nabiha Saklayen is using AI and ML to automate stem cell production, for stem cell-derived regenerative medicines for Parkinson’s, diabetes, heart disease and many more. Cellino’s platform combines label-free imaging and high-speed laser editing with ML to automate cell reprogramming, expansion and differentiation in a closed cassette format, enabling thousands of patient samples to be processed in parallel in a single facility, combining biology, laser physics, gene editing tools and ML.
Cellino, a closed loop cell therapy manufacturing company, has raised so far $96M by Leaps by Bayer, 8VC, Humboldt Fund, Felicis Ventures and Khosla Ventures. Khosla Ventures apart Cellino, has invested also in
CellFE, that has developed a scalable, high throughput microfluidic technology for the efficient delivery of gene-editing molecules into cells,
Bionaut, developing microscale robots to deliver biologics or small molecule therapies locally to targeted disease areas and
Liberate Bio, using automation, in vivo high-throughput screening and ML to accelerate discovery of novel extrahepatic delivery vehicles.
🟢 Rubik Therapeutics, founded in 2020 by Murray Robinson, is leveraging its proprietary computational platform to identify novel tumor antigens and map immune cell signaling pathways, to develop cell therapies that target highly selective, unique solid tumor targets.
🟢 Twist Bioscience founded in 2013 by Emily Leproust, Bill Banyai and Bill Peck, is developing a proprietary semiconductor-based synthetic DNA manufacturing process featuring a high-throughput silicon platform that allows to miniaturize the chemistry necessary for DNA synthesis.
In 2021, Twist Bioscience incorporated the MOLCURE AI technology to augment therapeutic antibody discovery. MOLCURE's patented and validated AI platform is based on evolutionary molecular engineering, next-generation sequencing (NGS) and laboratory automation technologies.
In 2023, Twist Bioscience announced the launch of Twist TCR libraries and Twist CAR libraries that provide researchers with the ability to rapidly create custom libraries that can enable the identification and development of next generation cell therapies.
In 2024, Twist Bioscience and Element Biosciences (developing DNA sequencing and other omics technology for research markets) announced a collaboration to develop the Twist for Element, Exome 2.0 plus Comprehensive Exome Spike-in Workflow for Element’s AVITI™ System, that will offer customers an economical and streamlined approach to next generation sequencing
Twist Bioscience has raised a total of $321M over 11 rounds.
🟢 Exogene (founded in 2019, Oxford, UK), combines AI, high-throughput TCR-cell screening and deep sequencing to mine the immune system for rare, natural TCRs against novel targets, that uses to develop its own pipeline of TCR-based cell therapies. In particular, they sequence TCRs (the T-cell receptor, TCR, is a protein complex found on the surface of T cells, or T lymphocytes) from patient derived cells to generate trillions of TCRs in silico. Then with a comprehensive screening with AI they identify novel TCRs against cancer targets of interest.
In 2022, Exogene secured $2M to advance its AI platform for solid-tumor cancer cell therapies. The founders are Federico Paoletti and Andrea Mambrini.
🟢 The British techbio innovator Etcembly, established in 2020 by Michelle Teng and Jacob Hurst, is developing the next generation of immunotherapies with a pipeline of best-in-class T cell receptor (TCR) therapeutics designed using generative AI. TCRs constitute one of the most promising classes of emerging therapeutics, although TCRs are amongst the most complex facets of immune biology.
Etcembly is building the world’s largest ML database and unmatched immunology expertise to deliver the safest and most powerful TCR immunotherapies through rapid computer-assisted engineering. Their platform EMLy™ uses generative large language models to rapidly predict, design and validate TCR candidates (with deep sequencing). EMLy™ scans hundreds of millions of TCR sequences then engineers them to achieve low pM affinity and eliminate cross-reactivity. The company’s lead therapeutic programme, ETC-101, is an AI-designed bispecific T cell engager that targets PRAME, an antigen present in many cancers but absent from healthy tissue. Etcembly has advanced ETC-101 to this stage (lead optimization) in 11 months, compared with 2+ years for conventional TCR discovery and engineering pipelines.
🟢 In 2021, LatchBio emerged from stealth mode providing almost code-free biocomputing solutions on the cloud that can be accessed from anywhere via a browser to simplify biological data analysis. Using their platform, researchers can upload files and access dozens of bioinformatics pipelines and data visualization tools from analyzing RNA sequencing data to designing CRISPR edits and even running the AlphaFold software just from their laptop.
Regarding immunomodulation, fine understanding of immune cell phenotypes and T-/B-cell specificities is very important and these processes rely on TCR/BCR complex discovery and characterization. Previously a laborious multi-year endeavor, this process can now be condensed into a matter of weeks by single-cell genomics: paired ɑ/β TCR sequencing at Latch.
LatchBio founded by Alfredo Andere, Kenny Workman and Kyle Giffin has raised a total of $33.2M. For more follow them on Substack: LatchBio
🟢 Jura Bio founded in 2017 by Elizabeth Wood and Julie Norville, is developing immune-based therapeutics using ML and synthetic biology. With their ML-guided end-to-end discovery and development platform, they harness a combination of synthetic biology and probabilistic ML to help them design, build and test the next generation of genomic medicines at extraordinary scale. On September, 21, 2023, Jura Bio has entered a research collaboration with Syena, a cell therapy product company and subsidiary of Replay, to develop T cell receptor (TCR) based therapies (such as KRAS G12D). Jura Bio has raised $16.1M.
Berkeley Lights, now part of Bruker Cellular Analysis, provides AI solutions for antibody discovery, cell line development, cell therapy development and synthetic biology for life science research.
AI and gene therapy with adeno-associated virus (AAV)
🟢 Dyno Therapeutics founded in 2018 in US, is transforming the gene therapy landscape with AI-powered AAV vectors. Dyno launched Dyno bCap 1™ capsid product, a breakthrough central nervous system (CNS)-targeted AAV gene delivery vector that provides dramatically improved CNS delivery—since delivering genes to the brain has been an elusive goal due to the blood-brain barrier—and liver detargeting—when compared to leading natural capsids—and stronger all-around characteristics relative to other engineered CNS-IV capsids. And in 2023, Dyno launched Dyno eCap 1™ capsid product, a leading eye AAV gene delivery vector that provides significantly improved delivery to the eye compared to other externally engineered capsids, including transduction throughout multiple layers of the retina. Dyno_Tx places a big emphasis on collaboration, and already has partnerships with Roche, Astellas Pharma, Novartis, Spark Therapeutics and Sarepta Therapeutics.
In 2021, Dyno Therapeutics Closed a $100M Series A Financing Led by Andreessen Horowitz (for a total of $109M over 2 rounds). The company was founded by Eric Kelsic, Adrian Veres, Sam Sinai, George Church and Alan Crane.
🟢 Always in relation to AI and AAV gene therapy, on November 8, 2022 Cyagen—the world's largest provider of custom-engineered mouse and rat models offering also stem cell products, including cell lines, media, and differentiation kits—and the clinical-stage Neurophth Therapeutics have entered a strategic partnership to jointly develop next-generation AAV gene therapy vectors (the adeno-associated virus/AAV vectors are the leading platform for gene delivery) for specific kinds of genetic ophthalmic ailments. Neurophth (founded in 2016) is China's leading in-vivo gene therapy company for ophthalmic diseases.
Utilizing AI and single-cell RNA-sequencing technologies, Cyagen’s high-throughput AAV vector discovery platform helps overcome the present limitations of gene therapy R&D by quickly identifying next-generation AAV capsids that have enhanced tissue targeting capability, tissue specificity, and productivity. Cyagen has produced substantial experimental data for AI model training and developed proprietary ML algorithms to accelerate the AAV capsid identification and optimization processes compared to traditional directed evolution methods.
For the more: AI Tools for Cell and Gene Therapy (2nd part).
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