Animation on our approach and opti-ox
bit.bio is based on a new paradigm in biology. We look at a cell as if it were a computer. In this paradigm, the nucleus is the hard drive and stores genes in its DNA. Genes interact with each other to create programs called gene regulatory networks (GRNs); together these programs form LifeOSTM, the Operating System of LifeTM. At any particular moment in time, only a subset of these programs are active. These determine the function and identity of a cell.
The activity of genes and their related GRNs is controlled by transcription factors (TFs). These are the ‘code words’ of LifeOS. A unique combination of 1-6 TFs defines the identity of every cell.
Our precision cell programming technology opti-oxTM enables deterministic activation of TF codes to program new cell identities. opti-ox reprogramming overcomes the ultimate barriers of cell manufacturing and enables precise, rapid (one order of magnitude faster) and scalable generation of pure human cell types.
Our technology would not exist without significant breakthroughs and the paradigm shifting work of many other scientists. They enabled the new paradigm: biology as software.
The first cell reprogramming protocol dates back to 1980 when Weintraub and colleagues discovered that the activation of a specific gene is able to turn a connective tissue cell into muscle.
Subsequently, the work of Nobel Prize laureates Shinya Yamanaka and Thomas Südhof and the inspiring science of Marius Wernig and the broader field confirmed that transcription factor codes determine the identity of cell types.
Reprogramming opens the door for manufacturing of cells an order of magnitude faster than conventional stem cell approaches and with increased precision.
Using opti-ox™ reprogramming stem cells into functional skeletal muscle (9-day time course; final contraction assay by addition of acetylcholine)
opti-ox - optimised induced overexpression - is a precision cellular reprogramming technology that enables faithful execution of genetic programs in every cell.
Our proprietary opti-ox approach makes use of specific locations in the DNA called genomic safe harbour sites to overcome gene silencing.
These are evolutionary conserved locations in the genome that protect the integrity of the cell and the inserted program. This overcomes the problem of gene silencing, and enables the safe and deterministic reprogramming of pluripotent stem cells into target cell types and ultimately pure and highly defined and functionally mature cells to be generated at a commercial scale.
Scientifically speaking, these results indicate that to deterministically reprogram pluripotent stem cells it is necessary and sufficient to control the expression of reprogramming factors.
Our opti-ox patent protects the use of inducible gene expression cassettes driven from GSHs in mammalian cells.
Learn more about opti-ox in this blog post.
The human DNA contains approximately 2000 different transcription factors.
Empirically, we know that between 1 and 6 transcription factors are required to reprogram a particular cell type. Identification of new reprogramming protocols therefore represents a high-dimensional combinatorial problem. Every human cell type, including sub-cell types and even cellular states, are defined by their own unique combination of transcription factors.
bit.bio’s Discovery Platform combines big data, machine learning and large-scale experimentation to find the combination of transcription factor codes for every human cell type.
It also allows us to address the final frontier of cell manufacturing: we can precision engineer the function of cells, including their maturity.