How We Could Treat Diseases With Biocomputers
What if your body could monitor itself to detect and treat diseases before symptoms even manifest?
Well, your immune system already does that (to an extent)! Your immune system is constantly protecting you against disease and infection and helping you recover after injury.
As soon as our body has trouble fighting off a disease, we might head to a doctor for a diagnosis, take medication for a cure, or rely on other forms of treatment (therapy, surgery, etc.) for restoration to health. But, many people are asymptomatic for a long time and symptoms often only make themselves evident after a condition has gravely deteriorated. It might be too late for optimal treatment by the time we’re aware of an internal problem.
Because biological computers could detect disease indicators and provide therapeutic relief, they could act as living medicines and prevent the worsening of disease in your body! These nano-machines
Because biological computers could detect disease biomarkers as input signals to provide a diagnosis or therapeutic relief, they could act as living medicines and prevent the worsening of disease in your body.
WHAT ARE BIOCOMPUTERS?
Put simply, biological computers (or biocomputers) are computers composed of biological parts (think of DNA or proteins). Biocomputers are capable of storing and retrieving data, performing and carrying out computational tasks, and controlling and modulating biological systems. Scientists can engineer biomolecular systems to interact and computationally function like a classical computer.
The biological computers we design could be the control systems for engineered living organisms.
WHAT ARE LIVING MEDICINES?
A living medicine is a biopharmaceutical that treats disease in a pretty unique way… it consists of a living organism! Genetic engineering is used to provide therapeutic properties to a cell or virus, which is then injected into or orally-administered by a patient as a living medicine.
Cellular, phage, and bacterial therapeutics are all examples of living medicines.
It possible to engineer living medicines with specific genetic and molecular components to treat disease, perform a specific function, and have therapeutic properties. By engineering switches and synthetic biological circuits in bacteria, living medicines could activate, inhibit, or control activity to treat disease.
HOW TO BUILD LIVING MEDICINES?
Building living medicines is an exciting research area between synthetic biology and microbiology.
A biopharmaceutical is a drug extracted from biological sources or manufactured in living organisms. Starting from bacteria, yeast, and mammalian cells, biopharmaceuticals include vaccines, allergens, donor blood, somatic cells, gene therapies, tissues, recombinant proteins (which are made up of genetic material from different sources), and living medicines.
Biological processes are involved in the semisynthesis of biopharmaceuticals. To semisynthesize is to isolate chemical compounds from natural sources (products of a living organism, found in nature) and use them as the starting chemicals for new compounds with different properties. Whereas total synthesis creates a target molecule from synthetic starting materials (such as petrochemicals or minerals), partial chemical synthesis produces a novel compound from existing ones with often more complex and fragile structure and functionality.
Semisynthesis is cheaper than total synthesis because fewer chemical steps are necessary.
When used in drug discovery, semisynthesis must retain the desired medicinal activity but can alter side effects and oral bioavailability in a few chemical steps.
Genetic circuits could be designed to have the ability to detect 2 distinct biomarkers as inputs and produce 2 distinct outputs, one that indicates the presence of disease and another that administers healing effects. If a first input is thus active, the biocomputer could, for example, activate a visual signal as an output to make the presence of disease evident. If 2 biomarkers are active, the biocomputer could also produce a therapeutic output to treat the disease.
In “A CRISPR/Cas9-based central processing unit to program complex logic computation in human cells”, a paper by Hyojin Kim, Daniel Bojar, and Martin Fussenegger, a core processor based in CRISPR-Cas9 was introduced, which could take various guide RNA (gRNA) inputs to program a transcriptional regulator (dCas9-KRAB) and thus, perform computations.
Because conventional biocomputers in single cells often consist of multiple protein-based gene switches (regulatory ON/OFF switches in natural genetic circuits), their programming is limited in flexibility and complexity. A CRISPR-CPU (CRISPR-based computer processing unit) was developed, whose core processor is a Cas9-based transcriptional regulation system and synthetic gene circuit uses gRNAs and corresponding promoters.
SOCIAL CONCERNS & TECHNOLOGICAL CONSTRAINTS
It would be unwise to blindly implant biocomputers in humans without putting safeguards in place to prevent the accidental production of medication. The more chemicals and input signals that are used to trigger drug production, the better, because the biocomputer is hence less likely to activate production at the wrong time or place. The safeguards could be composed of robust logic gates that would wait for sufficient, appropriate signals before producing drugs.
To avoid the escape of living medicines from the body or complications within the patient, living medicines also must be engineered to remain in the patient for a fixed duration or until they’ve completed their task. Furthermore, there is little information about the interactions between the engineered biocomputers and complex bacterial communities. Researchers and scientists are now focusing on the containment of biocomputers and the synthetic and natural biological circuits in organisms that produce therapeutic effects for living medicines.
Depending on the intended use of a living medicine, it will either consist of DNA molecules and bacteria, or mammalian cells. A synthetic circuit in a microbe might be easier to engineer, but harder to implant in a human than a synthetic circuit in mammalian cells.
“In order to be of any therapeutic relevance in the future, you need to establish these things in mammalian cells,” believes Martin Fussnegger.
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