5 Novel Therapies Using Synthetic Biology
The 1997 film “Gattaca” promised a future where humans would be free of disease and babies born on demand with the latest upgrades, including enhanced speed, intelligence, and beauty. Much like a new Tesla Roadster. However, despite the technological predictions offered by Hollywood moviemakers, we’re still living in a time when synthetic biology is working hard to make a dent in the world. No designer babies in sight. And stem cell technology promised so many radical breakthroughs back in the late 1990s, including growing organs for transplants and regenerating whole body parts, but the challenge of growing whole organs has been shown to be more complex than previously believed, including technologies like 3D bioprinting and xenotransplantation.
Despite the challenges and setbacks, investors believe we’re living in a different time, with more money pouring into the space over the last few years:
Indeed, the science and technology behind manipulating biological matter are still promising when it comes to health and medicine, especially with the rise of CRISPR gene editing. The idea that we could potentially switch on or off genes that cause disease using a cocktail of enzymes is just fantastical. While inserting CRISPR enzymes into a live human being is a bit challenging, there are regions of the body that are easily accessible, such as the eye. In a landmark clinical trial approved by the FDA and led by Editas Medicine (EDIT) and Allergan, now owned by AbbVie (ABBV), a CRISPR-Cas9 gene therapy was administered directly to patients to remove rare mutations that can cause childhood blindness.
McKinsey is calling this emerging technological renaissance the next Bio Revolution, with advances in biological sciences being accelerated by automation and artificial intelligence. The speed at which scientists and researchers were able to sequence the genome of the ‘Rona virus is a testament to the power of these converging technologies. McKinsey predicts that synthetic biology could have a direct economic impact of $4 trillion per year, nearly half of which will be in the domain of human health.
Let’s take a look through five companies that are harnessing the revolutionary power of synthetic biology to design new therapies and treat human diseases.
Engineered CRISPR Enzymes
Founded in 2017 and headquartered in Alameda, California, Scribe Therapeutics is a biotechnology startup that is producing therapeutics using custom-engineered CRISPR enzyme technology. The company has raised a whopping $120 million from the likes of Andreessen Horowitz to build out a suite of CRISPR technologies designed to treat genetic diseases. Scribe Therapeutics was co-founded by Dr. Jennifer Doudna, the UC Berkeley biochemist who discovered and developed CRISPR gene-editing technology and won the Nobel Prize in Chemistry in 2020 for her pioneering work.
The team at Scribe Therapeutics has designed its X–Editing (XE) technology by evolving the native CRISPR gene-editing enzymes available to us to redesign and engineer them to suit different needs. More specifically, they want to be able to modify or silence the genes of live humans to treat genetic diseases such as Huntington’s, Parkinson’s, Sickle Cell Anemia, and Amyotrophic Lateral Sclerosis (ALS). Anything your parents unwittingly handed down to you, Scribe Therapeutics is looking to treat it. The research team tests thousands of redesigned enzymes and selects those with greater editing ability, specificity, and stability compared to current enzymes. Scribe Therapeutics is starting with a pipeline of therapeutics to treat neurodegenerative diseases and has its sights set on other, less common genetic conditions down the road.
Stem-Cell Derived Immunotherapies
Canadian biotechnology startup Notch Therapeutics was founded in 2018 and has raised $86 million to develop immune cell therapies against pre-cancer cells. The company’s cell therapies are based on induced pluripotent stem cells (iPSC), which are pre-differentiated cells with the limited capacity to transform into different mature cell lines. Based on its Engineered Thymic Niche (ETN) platform, the company is developing universally compatible stem cell-derived immune cell therapies.
Normally, human immune cells only recognize other cells found in the same individual and will target cells from other individuals, which appear foreign to the immune system. That’s why donor organs can sometimes be rejected by the recipient’s body – the immune system sees the organ as a foreign object. Notch Therapeutics is designing a system where the immune cells produced from the stem cells will be universally recognizable by all individuals, bypassing the need to create immune cells from pluripotent stem cells derived from each recipient. These manufactured immune cells, which include T cells or natural killer cells, can be programmed to target cancer cells and eliminate them from the patient.
Reprogramming Cells
Founded in 2016, Massachusetts-based bit.bio is a synthetic biology startup that’s working on merging the world of coding with biology. The company has secured $42 million after a Series A round that was completed in June 2020. A spinout of Cambridge University, bit.bio is looking to commercialize its proprietary platform, opti-ox, which can reprogram human stem cells to do its bidding cure diseases. Touted as the Cell Coding Company, bit.bio was founded by Dr. Mark Kotter, a neurosurgeon at the University of Cambridge who studied regenerative medicine and stem cell technology.
While the ability to program mammalian stem cells has been around since 1981, the company claims it can consistently reprogram human adult cells into pluripotent stem cells, and then transform them into other mature human cells within days. Currently, stem cell technology produces a statistical mixed bag of mature, differentiated cells, some of which can have potential side effects. opti-ox uses a precise combination of transcription factors to ensure stem cells mature into cardiac, muscle, liver, kidney, or lung cells with high efficiency. The holy grail for the company is to be able to produce every cell in the human body for any cell therapy safely, on-demand, and with purities approaching 100%. And we’ll be here, waiting for that stem cell therapy for erectile dysfunction promised by the medical community.
Synthetic Vaccines
Founded in 2020, Delonix Bioworks is a Shanghai-based synthetic biology company designing therapeutic solutions against infectious diseases. The startup received $14 million from a Seed round just back in March. The Delonix Bioworks team is focusing its initial efforts on anti-microbial resistant (AMR) infections. The emergence of resistance in some bacteria species against common antimicrobial compounds, so has led to an increasing number of infections that are difficult to treat with conventional strategies. These ‘superbug’ strains are mostly spread in hospital or clinical settings due to the overuse of antibiotics.
The company is engineering attenuated, live bacteria that can act as vaccines against these types of infections. By introducing reprogrammed, but weakened, bacteria to express specific antigens on the surface of their membrane that match those of the strains that cause AMR infections into an individual, the individual’s immune system can recognize those antigens and respond to future infections with greater speed. It’s no different from how antiviral vaccines are designed, except most vaccines introduce an attenuated or inactivated virus to activate the immune system instead. And for those of you who skipped high school biology, no, this is not a mind-control scheme orchestrated by biotech companies.
Synthetic Psychedelics
Founded in 2018, Octarine Bio is a Danish synthetic biology company that’s building out a pipeline for high-potency cannabinoids and psilocybin derivatives for the pharmaceutical industry. Octarine Bio has brought in $3 million after a Seed round that was also completed in March. Medical studies on psychotropic compounds have been shown to help reduce anxiety, depression, and pain, and may have the potential to serve as novel psychiatric medications. A few companies have recently emerged to commercialize existing psychedelics. Octarine Bio believes it can do better by harnessing the power of synthetic biology to engineer microorganisms to produce these psychotropic compounds with better pharmacokinetic and therapeutic effects.
Normally, natural products are produced by plant and fungal species as an ill-defined mixture. The psychoactive properties of these compounds primarily stem from only a handful of compounds because their natural concentration is much higher than other derivatives in the organic material. For example, tetrahydrocannabinol (THC) is the main psychoactive agent in marijuana while psilocybin is the one found in mushrooms from the Psilocybe and other psilocybin-producing genera. However, these are just a few out of hundreds of potential psychoactive derivatives produced by these species.
Molecular derivatives may be produced at too low of concentration to test and analyze, or the plant or mushroom may have a deactivated metabolic pathway that could lead to a superior compound. By tweaking the molecular structure of the product compounds using both synthetic biology and traditional organic chemistry, the team at Octarine Bio is creating a platform to discover new potential therapeutics that may not have been available before. Magic mushrooms are about to get an upgrade for an extra potent trip.
Conclusion
Much like what was said about software by Marc Andreessen back in 2011, synthetic biology is starting to eat the world. While we’re a long way away from a dystopian future where babies are engineered with supernatural talents, we’re already seeing the potential side-effects of using CRISPR on the Chinese twin girls originally to immunize them from HIV, including enhanced cognition and memory. The cure for stupid is possibly lurking in the vaults of this pioneering technology. For now, we’ll wait and see how synthetic biology and CRISPR gene editing shape up as potential therapeutics for real diseases.
