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Biotechnological innovations have grown steadily in the past 10 years, not only in the medical arenas but also in agriculture, environment, and energy sectors. Almost all of these biotech innovations involve genetic engineering, diagnostics, or assays, reflecting on the importance of synthetic biology on current biotechnological developments. Here are the top 10 biotech innovations that are transforming the industry.
1. Single cell technologies
Single cell technologies provide detailed views of cellular environments and are important tools used in drug discovery and clinical research. Together with next generation sequencing, single cell technologies reveal a more realistic picture of a cell population, which is especially important in understanding the heterogeneity of the tumor environment. As these technologies are mainly used in the research setting, a number of contract research companies offer single cell sequencing and analysis platforms with specific DNA panels. For example, Mission Bio offers their Tapestri Platform for researchers to genetically profile each cell in a given population using a two-step microfluidic workflow combined with single cell sequencing . Disease-specific profiling can be achieved by using specific DNA panels, such as the acute lymphoblastic leukemia panel . Single cell analyses usually require multiple machines with separate protocols but Berkeley Lights has taken a step further by developing a single machine that can process and analyze cells one-by-one, simultaneously. The Beacon is capable of multiple single cell manipulations in one optofluidic chip containing tens of thousands of tiny cell chambers . By using light induced dielectrophoresis, specific cells are partitioned for further analysis, such as antibody repertoire screening as demonstrated by the drug discovery company, Aldevron [2, 3]. The Lightning was also recently launched to cater to T-cell specific research .
2. Aptamer biosensors
Glucose monitors, pregnancy tests, and heavy-metal sensors are just a few of the biosensor-based detectors developed and used since the 1960s . Biosensors consist of enzymes, antibodies, or microbes that enable a readout of the compound that is detected. Newer sensor technologies have focused on nucleic acid aptamer-based methods as they have the potential to be more sensitive, stable, and cost effective than earlier methods. Aptamer biosensors are typically developed by systematic evolution of ligands using exponential enrichment (SELEX,), which generate stable DNA or RNA molecules that are highly selective to its target. For environmental testing or medical diagnostics where sample complexity is high, aptamers might just be the right type of molecule and a number of companies have focused on developing aptamers for these purposes. For example, South Korea-based Aptamer Sciences has developed an in vitro diagnostic test called the AptoDetect-Lung that assesses the risk of a patient developing lung cancer by detecting seven lung cancer biomarkers . The test was shown to improve diagnostic accuracy compared to CT scan examination . AptoDetect-Lung was recently granted diagnostic approval by the Korean Ministry of Food and Drug Safety .
3. Current cell therapies
Management of chronic illnesses sometimes requires repeated drug treatments but imagine if there was a way for drugs to be delivered where it needs to be, when it is needed, automatically. This is where scientists are developing drug delivering cell therapies . In type-1 diabetic patients, impaired pancreatic β-cells lead to insulin deficiency and a build up of blood glucose, resulting in symptoms such as frequent urination, excessive thirst, and headache . A possible solution is being developed by Seraxis: an implantable device composed of lab-grown pancreatic cells that directly respond to a patient’s blood glucose levels . The device contains islet cells manufactured from induced pluripotent stem cells (iPSCs) and is intended to eliminate drug treatments for these patients. Another company currently developing implantable one-time treatments is Auckland-based Living Cell Technologies. Their NTCell therapy consists of an alginate-coated capsule containing neonatal choroid plexus cells that is implanted into the brains of Parkinson’s patients . Choroid plexus cells supply cerebrospinal fluid, mitogens, and other factors that support neuronal growth and function . In 2013, Living Cell Technologies sponsored the world’s first clinical trial for regenerative cell therapy for Parkinson’s disease and is currently evaluating NTCell for further studies.
4. Stem cell applications
Since the early 1980s, scientists have been studying the conditions and controlling the identity of which stem cells differentiate. The ability to generate the desired cell type by controlled differentiation proved to be industrially important in areas such as drug development, regenerative medicine, and the manufacture of valuable bio-materials. For example, one Canadian-based company, NovoHeart, developed a solution for researchers looking to conduct drug tests for cardiac diseases. Their MyHeart platform utilizes iPSCs to generate human cardiac tissue or organ models, such as their human ventricular cardiac organoid chamber (or human heart-in-a-jar), which more closely mimics the actual human heart environment than animal models typically used during preclinical development [13, 14]. MyHeart is intended to predict, more accurately, the effects of new drugs before they head to clinical trials. Another company is focused on bringing stem cell technology directly to the point of need. Platelet BioGenesis, a 2014 startup based in Massachusetts, is developing an on-demand, mobile bioreactor for in-field cell therapy, such as in military medical posts [15, 16]. The bioreactor manufactures iPSC-derived platelet-like cells that are currently being developed to treat blood-clotting diseases like immune thrombocytopenia .
"By integrating @Harvard's valved bioreactor technology with our own proprietary human heart-in-a-jar, Novoheart will advance its disease modeling capabilities to an unprecedented level of biofidelity for in vitro human cardiac assays" – Kevin Costahttps://t.co/zBwXX48EPL
— Novoheart (@Novoheart) December 19, 2019
Stem cells technologies are certainly not limited to medical research and treatments, and this is shown by the number of companies investing in cultured meats and alternative protein. Using cellular agriculture, companies like Future Fields, Memphis Meats, and Super Meat are developing lab-grown chicken, beef, duck, eggs, and milk. The first hamburger patty was produced in 2013 in Mark Post’s lab at Maastricht University, but for the colossal price of around $300,000 USD [17, 18]. Since then, companies have raced to reduce the manufacturing costs with Israel-based Super Meat potentially leading the race: the launch of the first lab-grown chicken tasting menu this October at their restaurant, The Chicken [19, 20].
5. CRISPR-based platforms
Since the discovery of the Streptococcus pyogenes CRISPR-Cas9 adaptive immune response by the groups of Jennifer Doudna and Emmanuelle Charpentier , both of whom are this year’s Nobel prize recipients in chemistry, a number of CRISPR-based companies have been established. However, the first commercial application actually began in 2007 when scientists at Danisco (acquired by DuPont in 2011) discovered short repeat sequences in the genome of one of their yogurt bacteria, Streptococcus thermophilus [22, 23]. They identified that these were clustered regularly interspaced short palindromic repeats (CRISPR), used by S. thermophilus to fend off bacteriophage infections . Dupont later used their discovery to engineer phage-resistant strains in their yogurt making process [22, 23]. Roughly a decade after, various CRISPR-Cas systems have been characterized, down to the atomic structure, with CRISPR-Cas9 being the most widely studied.
The trend of developing industrially important organisms has continued to this day and, using CRISPR-Cas9 technology, is faster than ever before. Synthetic Genomics, in partnership with Exxon Mobile, is developing CRISPR-edited microalgae with enhanced lipid output, which would improve oil manufacturing by potentially reducing CO2 emissions and reliance on fossil fuels [24, 25]. PLANTeDit and Toolgen are using CRISPR-Cas9 to engineer sustainable crops such as soybean without introducing foreign DNA . This is called DNA-free genome editing and although their crops will be modified genetically, they would bypass the regulatory hurdles of GMOs .
The first companies to enter human clinical trials with a CRISPR-based therapeutic were CRISPR Therapeutics and Vertex Pharmaceuticals in 2018 [27-29]. CTX001 is an ex vivo therapy being investigated for the treatment of β-thalassemia and sickle cell anemia . The therapy involves extracting patient blood stem cells, gene modification using CRISPR-Cas9, and reintroducing the cells back into the patient. Although clinical evaluation of CTX001 is still early, preliminary results (presented this June) showed potential benefits of the treatment in patients with hemoglobinopathies .
6. Directed evolution platforms
In 2018, Frances Arnold, George Smith, and Gregory Winter were awarded the Nobel Prize in chemistry for their research in the directed evolution of enzymes, peptides, and antibodies . Directed evolution platforms typically involve the generation of large, randomized genetic libraries that express variants of the gene of interest. These libraries are screened by selecting for those protein variants exhibiting desired properties such as increased ligand-binding or catalytic activity. This process is usually repeated by screening additional libraries based on the selected variants until a selection cut-off is reached. A number of protein-based therapeutics have been developed using this process: Humira (AbbVie), Lumoxiti (MedImmune), and Gamifant (NovImmune) .
One company has expanded on the directed evolution technology. Carmot Therapeutics, a drug discovery company based in Berkeley, developed the Chemotype Evolution platform to identify novel drugs. During Chemotype Evolution, a set of small molecules are linked to a proprietary fragment collection to generate a library of candidate drugs. The library is screened against a human target and selected candidate drugs are submitted to further rounds of linkage and selection until the candidate drug has evolved into an high-affinity binding molecule . Using Chemotype Evolution, Carmot identified two candidate compounds that are currently in clinical trials . Other companies are using directed evolution to generate microbial platforms. Primordial Genetics, a San Diego-based biotech, is developing a platform that produces large microbial libraries through combinatorial genetics called the Function Generator . Function Generator allows them to select for specific microbes that can potentially address a range of issues, from identifying stress tolerant yeasts for biofuel production to microbes capable of degrading plastics efficiently .
7. Microbiome-based innovations
In 2007, the United States National Institutes of Health launched the Human Microbiome Project (HMP) to provide funding support, reference databases, and other resources for microbiome research . Accordingly, the establishment of HMP fostered a bloom in research output along with a significant increase in funding aid . What was produced over the years were largely computational and statistical research tools (due to the huge datasets that were generated) and a number of microbiome companies. Many of these companies focused on human disease treatments, such as topical solutions that restore skin microbiome (AOBiome, ) or drug delivery using gut bacteria (Blue Turtle Bio, ), while some companies used microbiome technologies in other ways. Aster Bio developed the Environmental Genomics platform to assist their clients in monitoring liquid waste output and prevent contamination of natural water bodies . The platform profiles waste samples by detecting genetic biomarkers that are specific to key microbes, informs on potential operational issues (such as insufficient ammonia removal), and directs waste water treatment . Sunnyvale-based Floragraph is also examining waste but intends to bring microbiome analysis directly into the home . Their portable microbiome device is designed for customers who are interested in self-monitoring of chronic disease or track the health of companion animals by analyzing the microbiome from stool samples . Although it is uncertain how many people would want to analyze their own poop at home, the Floragraph brings portability, cost-efficiency, and accessibility to microbiome analysis. For in-field medical and research applications, this device might just fulfill the need.
8. DNA hard drives
We’ve come a long way from the early days of electronic data storage systems like the magnetic drum and floppy disks. Technological advancements have increased our data storage capacity by huge orders of magnitude, from tens of kilobytes (magnetic drum) to the petabyte range (cloud servers) . With this tremendous storage space also comes the need for tremendous physical space to house the server farms which support the cloud. Scientists first looked at using DNA molecules for data storage in 1988, with the insertion of 35 bits of ones and zeros encoding a 5 by 7 square-bit image into the E. coli genome [42, 43]. Since then, various institutions and corporations have invested their efforts into developing DNA-based data storage systems, given that cost, energy usage, and space is significantly reduced compared to that of maintaining server farms . Remarkably, it is estimated that storing all of the world’s data would compress into a mere 1 kg of DNA . So how does one ‘upload’ their photos or music into DNA? Scientists at the University of Washington and Microsoft tried to address this in their proof-of-concept study for an automated DNA storage system . They demonstrated that their device was able to encode a 5-byte “Hello” into a DNA sequence, synthesize, store, sequence the DNA and retrieve “Hello” . The entire process took 21 hours and would not be practical today to store a single photo. But given the speed at which such technologies are being developed, it will be no surprise to see it available in the very near future.
9. DNA origami
The base pairing of nucleotides in DNA and RNA make them an appealing biomolecular material with ‘self-assembling’ abilities. This was demonstrated by various groups in the mid-2000s [45-47], including Paul Rothemund who presented a method for assembling DNA into two-dimensional squares, triangles, happy faces, and other forms . In 2017, several research labs were able to construct the largest DNA nanostructures: large nanorods, bricks, and tiles that came together to form huge structures with lengths in the range of hundreds of nanometers to over a micron [49-51]. These studies present clear, 3-dimensional images of the DNA nanostructures showing that nucleic acids can be designed to assemble into any number of structures with application potential in medicine, electronics, and bio-materials. Currently, DNA origami is being developed to generate drug delivery platforms (Genisphere), diagnostic nanorobots (Nanovery), and enzyme-embedded nanofabrics for applications such as metabolite production (FabricNano) . Nanovery’s nanorobots are designed using artificial intelligence to detect circulating tumor DNA (ctDNA) . Their diagnostic nanorobot is intended to replace current liquid biopsy tests for ctDNA, which require extensive time and cost. The nanorobot is inserted into a blood sample and if cancerous DNA is detected, lights up within 1-2 hours. As mutations continue to accumulate in cancerous DNA, Nanovery intends to continuously evolve their nanorobots to detect these new mutations .
— Genetic Engineering & Biotechnology News (@GENbio) December 10, 2017
10. Artificial intelligence in medicine
Although artificial intelligence and machine learning are not considered biotechnologies, they deserve a mention due to their impact in the medical field. Research interest in AI-based medical applications has grown significantly over the past decade, as shown by the 20-fold increase in relevant publications from 2010 (596 papers) to 2019 (12422) . At the time of writing, there were a little over 70 market approved AI algorithms for medical applications, according to a study conducted by the University of Groningen and the Medical Futurist Institute [54, 55]. A number of these applications use image-based machine learning algorithms for the analysis, diagnosis, or assessment of disease. Qlarity Imaging’s QuantX software is an aid for radiologists to more quickly and accurately identify abnormal spots on breast MRI images . In a clinical study assessing the ability of a radiologist to correctly identify malignant lesions in MRI images, radiologists performed better when using the QuantX software . Research interest has especially grown for developing fully autonomous medical robots, which currently are being trained to complete very specific tasks. The IDx-DR device, developed by Digital Diagnostics, captures retinal images to diagnose diabetic retinopathy, a cause of blindness in diabetic patients . The images are analyzed by the AI machine trained to detect biomarkers such as protein deposits and exudates, and outputs a diagnostic report within 30 seconds. Efforts are also currently ongoing in developing fully autonomous surgical robots, at-home medical assistants, and mental health support robots.
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