bit.bio is a synthetic biology company working on producing every human cell type at scale, with the aim of transforming the research and medicine landscape. Farah Patell-Socha, PhD, VP Research Products tells Lu Rahman about some of the company’s groundbreaking work in this field and the benefits it is creating for disease modelling and drug discovery.
bit.bio believes that accelerated biomedical research, new generations of cures, and increased global sustainability are within reach when biology transitions to engineering. The company’s aim is to achieve this goal. It combines the concepts of coding and biology to provide human cells for research, drug discovery, and a new generation of medicines.
The company recently launched ioSkeletal Myocytes, human iPSC-derived muscle cells, to accelerate the study of human biology and disease. ioSkeletal Myocytes have been reprogrammed from human induced pluripotent stem cells (iPSCs) using the company’s precise reprogramming technology: opti-ox. These human muscle cells provide a powerful new tool for muscle research as well as research into diseases such as diabetes, mitochondrial disease, and muscular dystrophy. The product is the second in a wave of planned new cell types from the company that are set to supercharge drug development, disease research and new cell therapies.
Animal models still form the backbone of current drug discovery workflows, despite human biology often proving to be distinct. To overcome this, bit.bio is working to create physiologically relevant models that help drugs reach the market faster. “The lack of biological relevance in using animal models entails a huge opportunity cost in drug development. The average drug costs over $1.7 billion to bring to the market over a period of 13 years, with only a 3.5% probability of success,” says Patell-Socha. “We are at a critical time in biology where we have identified a huge bottleneck: a robust, consistent and scalable source of human cells. bit.bio will ultimately produce every type of human cell, at industrial scale. These cells will have an impact across the industry, potentially increasing the efficiency of drug development, while reducing the cost and time.”
ioSkeletal Myocytes, for example, have demonstrated similar drug response profiles to patient-derived primary cells, and because they can be consistently produced in large quantities, they can be used within high-throughput screening (HTS) assays. “HTS has long held promise as a method for fast-tracking drug development, it has thus far lacked the biologically relevant, consistent supply of human cells to deliver on that promise. With ioSkeletal Myocytes, drug discovery researchers can screen large compound libraries against a consistent disease model and identify promising candidates to take forward,” she adds.
The effort it takes to differentiate skeletal myocytes from human iPSCs using classical differentiation approaches is time-consuming and bit.bio has been working to create solutions to help speed up this differentiation. “Current processes for differentiating human induced pluripotent stem cells (iPSCs) to skeletal myocytes require complex protocols and expert professionals to feed and culture the cells daily for up to five weeks. Often, this does not lead to a desired homogenous and defined population of skeletal myocytes,” says Patell-Socha.
bit.bio’s proprietary opti-ox technology is designed to overcome these inherent limitations. The precise control of the expression of transcription factors results in deterministic reprogramming of entire human iPSC cultures into the target cell type.
“This process of converting human iPSCs into physiologically relevant contractile and multinucleated mature muscle cells that are reliable, reproducible and consistent at scale within days versus weeks is the innovative aspect of ioSkeletal Myocytes,” Patell-Socha adds. “Researchers can save significant time and effort compared to classical differentiation methods, focussing on their research versus protocols.”
Perhaps most importantly, reveals Patell-Socha, front-end validation and definition of myocytes is performed only once, rather than once for each new batch of primary cell lines. This translates to significant time and cost savings over the course of an extended research project.
There is of course a comparison to be made here with other methods of forward reprogramming. Patell-Socha explains: “opti-ox is bit.bio’s breakthrough technology, which enables the production of batches of every human cell type at scale and gives us the power to precision engineer human cells. It reliably activates specific transcription factors within the cells, providing the engineering tool to enable the scale level production of consistent cells.”
Indeed, the 2017 Stem Cells Reports publication Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes1, showed that opti-ox works reliably in producing neurons and myocytes, amongst other cell types, sparking consideration of cell therapies for the diseases that affect these cell types, as well as an existing demand from the community that researches these diseases. bit.bio commercialised the opti-ox powered ioGlutamatergic Neurons in 2019, and the ioSkeletal Myocytes in 2020.
There are clear benefits that ioSkeletal Myocytes bring to the drug discovery process compared with primary cells. Patell-Socha elaborates: “While primary cells are more physiologically relevant than animal models, they are difficult to produce in large numbers, and may lack reliability and consistency, especially over the course of a large study.
“ioSkeletal Myocytes have demonstrated similar drug response profiles and relevant bio-markers to patient-derived primary cells but can be produced at scale with consistency, entailing faster trials with human cells. This will allow researchers to discard unsuccessful drug designs earlier in the process, while progressing successful designs expeditiously. In addition, these cells may help in finally unlocking the potential of high-throughput screening (HTS) in the pharmaceutical industry.”
In addition to its current expertise, bit.bio – in its mission of coding cells for health – will be launching 20 further human cell products over the next three years with an initial focus on the central nervous, immune and muscle systems, opening new avenues of research and applicable technologies in each of these areas.
“We are also working closely with the pharmaceutical and academic communities to fast-track the development of specific disease models they most want to study and where there are unmet patient needs,” Patell-Socha adds.
“We believe having an unlimited supply of consistent cells will unlock the promise of cell therapies. Cells form a new generation of intelligent medicines, medicines that are personalised and precise and unlimited in their potential. That’s what the future looks like for bit.bio.”
Volume 22, Issue 2 – Spring 2021
ioSkeletal Myocytes, human skeletal myocytes generated by MYOD1-driven reprogramming of stem cells using opti-ox technologyBiography
Farah Patell-Socha, PhD, VP Research Products, bit.bio, builds industry defining products, setting standards in research & diagnostics. Her expertise lies in conceptualising, developing and launching products through strategic partnerships & KOL networks. Patell-Socha has a PhD in molecular biology from Cambridge and a postdoc in muscle stem cell biology. At bit.bio, Patell-Socha leads the product development pipeline with focus on product management & product marketing functions.
References
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390118/
