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Combining Coding and Biology To Engineer Human Cells

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bit.bio, a leading synthetic biology enterprise, aims to combine coding and biology to engineer human cells as a new generation of medicines using human induced pluripotent stem cells (iPSCs). Their current focus is on developing scalable technology capable of producing consistent batches of every human cell using principles of stem cell biology, cellular reprogramming, mathematical modeling and cell therapy.

To learn more about new technologies being developed for drug discovery and cell therapy, Technology Networks spoke to Dr. Farah Patell-Socha, VP of research products at bit.bio, and Furqan Iqbal, senior director of information systems at bit.bio.

Molly Campbell (MC): Can you discuss the rationale behind combining coding and biology concepts to improve human cells used for research, drug discovery and cell therapy?

Farah Patell-Socha (FPS): At bit.bio we view the cell as if it were a computer, with the nucleus of the cell containing the DNA or the hard drive. Embedded within the DNA is the software which stores all the genetic programs. We know that by inputting a unique combination of genetic code into a cell’s DNA we can trigger a cell to reprogram into any cell type – the key is finding the right code and unique combination for each desired cell type.

We apply a newer, alternative approach to generating human cells, referred to as “precision reprogramming”. This next-generation cell reprogramming method utilizes bit.bio’s proprietary opti-ox™ platform, featuring systematically optimized and inducible gene expression to input the right code into stem cells, telling them to change into a specific human cell type. opti-ox enables unlimited batches of any human cell to be manufactured consistently at scale, overcoming many of the challenges faced by traditional cellular reprogramming methods such as directed differentiation and cellular reprogramming.

By leveraging precision reprogramming, we have been able to produce two cell types at an industrial scale already: skeletal muscle cells and neurons, which are available for researchers to use “off-the-shelf”. Our cells provide a physiologically relevant in vitro model for research and drug discovery that is reliable and consistent across batches meaning that scientists can be more confident in their experiments.

MC: Why have previous methods to generate human iPSC-derived cells perhaps fallen short or had limitations?

FPS: The ability to generate human cells derived from iPSCs has been revolutionary for the scientific industry, offering a physiologically relevant model system and theoretically providing an infinite and renewable source of human cells for research, drug discovery and cell therapy. However, current methods to generate cells from human iPSCs (directed differentiation and cellular reprogramming) can be hindered by long complex protocols and lack reproducibility and scalability. 

The inconsistencies and inefficiencies of current cell generation methods mean that scientists are struggling with long experimental timelines and invariably battling variance in their datasets.

MC: How do bit.bio’s platform and products enable reproducible scientific research?

FPS: In laboratories around the world, there is no standardized way of procuring and experimenting on human cells. This means that conditions vary wildly across academic establishments, biopharmaceutical companies and countries, and therefore results can be hard to reproduce under different conditions. Cells in different conditions, derived in different ways, can produce wildly different results, which impacts our scientific understanding of basic biological processes and can also impact pharmaceutical pre-clinical trials too. This can lead to bad or inaccurate science being published in even the most respected scientific journals.

With human iPSC-derived cells powered by opti-ox, we can create a universal reference standard for future biological research. Other fields of science are unified by common units, whether it be “inches” or “millimeters”, and these can be easily converted from one to the other. By applying engineering principles to biology, we can create the equivalent of the “millimeter” for research in the life sciences, a universal metric by which all research can be judged.

MC: Can you discuss the applications of bit.bio’s cells and how they are being utilized by customers working particularly in drug discovery and cell therapy?

FPS: bit.bio cells are already being used by top biopharmaceutical companies around the world to accelerate their research, which will help develop the treatments of tomorrow. We have recently launched our ioDisease Model cell portfolio, having announced our first product – a Huntington’s disease model – last month. By combining genetic engineering technology like CRISPR in combination with our opti-ox technology we have been able to develop not only wild-type human cells, but also those that express the specific genetic aberrations that lead to neurodegenerative and muscular conditions. With these cells, researchers are being armed with the best tools to target debilitating and sometimes fatal diseases, affording deeper insights at the pre-clinical stage that has the potential to accelerate drug discovery and development over the coming years. This is just the first in our pipeline of disease models, many of which will be rolled out in 2022.

The ability to produce large amounts of specific human cells also opens huge possibilities for cell therapies. Cell therapies involve transfusing or transplanting human cells into a patient to repair damaged tissue or boost bodily functions like immunity. Previously cell therapies have been bespoke and expensive, tailoring individual treatments to individual patients which takes vast amounts of time and resources. A pre-made and pre-programmed treatment of human cells democratizes access to this next generation of medicine, making it available to more people at affordable costs.

MC: What is bit.bio’s vision for the Lab of the Future, and how does its products and services align with this?

Furqan Iqbal (FI): This is going to be all about data – the future starts by leveraging a single platform that will enable access to all available data assets. The adoption of the laboratory information management system (LIMS) will improve lab productivity and efficiency by keeping track of data associated with samples, experiments, workflow and instruments. A single source of truth that will enable reliable and detailed searches on demand which will link colleagues, equipment, consumables and data.

The acquisition of data will be further enhanced through direct integration with laboratory hardware thereby minimizing reliance on manual transfer of data. With the massive volumes of data expected, our lab of the future will introduce advanced analytics and modalities to drive actionable insights, enabling us to make data-informed business decisions. Our moonshot goal is leveraging our discovery platform and opti-ox for the production of every type of human cell. If we achieve this, access to accurate and physiologically relevant cell models would no longer represent a bottleneck in therapeutic discovery and disease research.

Farah Patell-Socha and Furqan Iqbal were speaking to Molly Campbell, Senior Science Writer for Technology Networks.