Scientists at King's College London and bit.bio Collaborate to Develop Multi-Cell Models of the Human Brain With Optimised Open-Source Protocols for Use by Any Researcher

• Three different products from bit.bio’s ioWild Type Cells^TM range will be combined to create multi-cell models that are consistent and scalable for more relevant representations of neuron-microglia interactions
• Novel multi-cell models of the brain are vital to progress scientific understanding, screen for new treatments and develop novel therapies for neuronal and psychiatric disorders such as schizophrenia
• Collaboration plans open sharing of scientific protocols and methods to provide novel multi-cell models of the brain to researchers worldwide

bit.bio, the company coding human cells for novel cures, and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London today announce a collaboration to build multi-cell models of the human brain using bit.bio’s ioCells™️.

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Professor Deepak Srivastava and Dr Anthony Vernon will create different bi- and tri-cell models by combining three ioWild Type Cells - ioGlutamatergic Neurons™️, ioGABAergic Neurons™️ and ioMicroglia™️. The cells have been precision reprogrammed from induced pluripotent stem cells (iPSCs) using bit.bio’s opti-ox™️ technology, meaning they are consistent at scale.

The human brain is made up of numerous different cell and sub-cell types. Subtle defects in one cell type can unbalance this highly-connected system and give rise to neuronal and psychiatric disorders. Multi-cell models are therefore essential to reveal some of the more complex aspects of a disease that cannot be studied in mono-culture systems. Furthermore, alterations in the functional properties of one cell type may impact the ability of a second cell type to work correctly; such interactions can only be studied using a multi-cell model.

Professor Deepak Srivastava PhD, Professor of Molecular Neuroscience at King’s IoPPN, Group Leader MRC Centre for Neurodevelopmental Disorders and Director of the Wohl Cellular Imaging Centre said:

“It’s the unique properties of bit.bio’s ioCells that will enable us to create a consistent and scalable multi-cell model. Both Dr Vernon and I have used ioCells extensively in our work and have seen first-hand the consistency they offer. These properties significantly reduce potential concerns that variability in experimental data could be due to variation in the cells in our models. Once we have created our multi-cell models with ioCells we expect they will provide a useful reference for use across the scientific community and enable breakthroughs in our understanding and treatment of neuronal and psychiatric disorders.”

Professor Srivastava and Dr Vernon will run different experiments to find the correct ratios of each cell type and the most appropriate conditions to create optimal co-culture models. Once the protocols have been developed, they will be shared with the wider scientific community for use across research and drug discovery.

Dr Anthony Vernon, a Reader in Neuropsychopharmacology at King’s IoPPN and Group Leader at the MRC Centre for Neurodevelopmental Disorders said:

“The neurobiology of psychiatric disorders with a putative neurodevelopmental origin, including schizophrenia, remains incompletely understood. Whilst antipsychotic medications can be effective, they do not address all symptoms of schizophrenia and a significant proportion of individuals show no therapeutic response to these agents. Moreover, they are associated with significant side effects. As such there is a clear need to develop novel treatment strategies, for which novel, human in vitro cellular model systems will be extremely useful in the context of drug screening and functional genomics approaches.”

Professor Srivastava and Dr Vernon will also use the models in their own research and will have access to the Wohl Cellular Imaging Centre at King’s College London – an advanced light microscopy centre that has a focus on neuroscience research. At the centre, co-culture systems can be characterised at scale and with remarkable resolution (for instance at the synapse level) that could allow identification of novel biological mechanisms of cell type interaction in the central nervous system and open new avenues for treatment.

Farah Patell-Socha, VP Research Products at bit.bio said:

“We are delighted to be working closely with the team at King’s College London to develop these new multi-cell brain models, which aim to further advance our understanding of neurodevelopmental disorders and other mental health problems. Collaborations such as this between academia and industry, which bring together expertise, share knowledge, build trust, and lead to new research tools and protocols for the benefit of the scientific community, are vital for the advancement of research and drug discovery.”

The collaboration will run for three years, initially developing models using the three ioWild Type products. bit.bio and the team at King’s College London also intend to incorporate ioDisease Model Cells™ - with gene edits that mimic what happens in a particular disease - into further multi-cell models of the human brain.

Notes to editors

The functions of the three ioWild Type cell types in this collaboration are:

1. Glutamatergic neurons - the excitatory neurons of the brain cortex. They produce glutamate, which is the main excitatory neurotransmitter in the mammalian central nervous system. Disorders affecting these neurons include schizophrenia, dementia and epilepsy.
2. GABAergic neurons - responsible for slowing down the propagation of the brain’s electrical signals. This function is essential for information to be efficiently relayed throughout the brain. GABAergic neuron dysfunction has been associated with a variety of psychiatric disorders and neurological diseases, including epilepsy, schizophrenia, autism and Alzheimer’s disease.
3. Microglia – classically thought of as immune cells in brain tissue, microglia play diverse roles from maintaining brain homeostasis to helping shape the formation and refinement of neural connections during brain development.

About bit.bio

bit.bio is a synthetic biology company focused on human cells that is advancing medicine (UN SDG9) and enabling curative treatments (UN SDG3). The company does this by industrialising the manufacture of human cells and making them more accessible. The company was spun out of the University of Cambridge in 2016 and has since raised approximately $200m from investors such as Arch Venture, Foresite Capital, Milky Way, Charles River Laboratories, National Resilience, Tencent, Verition Fund and Puhua Capital.

bit.bio’s opti-ox™ precision cell programming and manufacturing technology enables conversion of induced pluripotent stem cells (iPSCs) into any desired human cell type in a single step. This can be achieved within days and at industrial scale, while maintaining exceptional purity and unparalleled consistency.

Our discovery platform extends this approach to any desired cell type by identifying the transcription factor combinations that define cell states (including identity, cell subtype identity, maturity) using high throughput screens and advanced data analysis. We believe that opti-ox can revolutionise regenerative medicine similarly to how CRISPR is unlocking gene therapy.

bit.bio’s cell therapy pipeline, based on txCells^TM, is focused on serious diseases that lack effective treatments. Our current therapeutic development areas include metabolism and endocrinology, immunology and neurology. Our lead candidate, bbHEP01 based on txHepatocytes, is in development as a treatment for patients suffering from acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) and is expected to enter clinical development in 2025. Complementing our internal pipeline, we have a collaboration with BlueRock Therapeutics (a wholly owned independently operated subsidiary of Bayer AG) focused on regulatory T cell (Treg) based cell therapies.

In addition, our extensive ioCells™ research cell product portfolio, which includes wild type, disease model human cells and CRISPR-ready cells, is opening up new possibilities for studying human biology and developing new medicines in both research and high throughput and high content drug discovery.

For more information, please visit www.bit.bio

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience

King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.

The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn

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