R&D to build robust technologies to meet the pathogen challenge quickly and effectively
Accelerating R&D for pandemic preparedness and countering evolving pathogens
We invest in transformative, high-risk, high-reward technologies. We believe a dynamic problem such as evolving, emerging and drug-resistant pathogens cannot be solved using slow, linear approaches. Therefore, we are interested in developing dynamic, adaptable and innovative solutions.
To enable these, ARC will allow for low cost and rapid evaluation of ideas via partnering with academia, foundations, start-up and established industry.
Your support can make ARC a reality
Donate today to push our technologies through our accelerated pipeline and bring cutting edge therapeutics and diagnostic techniques to market at a fraction of the cost and far lower risk
FAST stands for Facile Accelerated Specific Therapeutic. As the name suggests, this is a novel therapy pipeline that is very fast. In less than 10 minutes, the FAST software designs a therapy that specifically attacks the pathogen of interest. This design can be synthesized in less than 4 days, then tested in less than 1 day, resulting in a complete therapy in less than one week. Traditionally, antibiotics and therapies take 5–10 years to develop.
The FAST Platform drastically changes the way modern medicine responds to emergent pathogens. Since FAST therapeutics are based on the same platform, once the platform itself is FDA approved, new designs don’t need to spend years going through the same process. We can produce medicine when we need it, enabling responses to pandemics and emergent infections in real time.
The COVID-19 pandemic has forced the entire globe to face a harsh reality: We are not prepared to handle pandemics. Infections and disease caused by emergent viruses or multidrug-resistant bacteria pose a grave concern to global health. Our current approach to developing new therapies takes billions of dollars and many years. Using this same pipeline to develop therapies that we need right now is not feasible or realistic.
The FAST Platform revolutionizes the way we treat infections by targeting genetic features unique to each pathogen. If we have the genome of the microbe causingthe infection, we can design, synthesize, and test a FAST therapy in 1 week.
A SUPER STRONG DNA TO BLOCK BACTERIAL VIRULENCE GENES
Peptide nucleic acids
Every living thing on Earth has its own DNA, a genetic code that tells each cell how to behave based on environmental and internal signals. This DNA is made up of nucleic acids, molecules that bind and interact in structured predictable patterns. Peptide nucleic acids, or PNA, take advantage of this predictability by mimicking the behavior of DNA with much stronger binding strength.
We can build a short PNA sequence that blocks a key DNA sequence of a pathogen. PNA can block its antibiotic resistance gene or its ability to produce a toxin, effectively turning off the virulence of a microbe, like putting super glue in the lock to the microbe’s house. This interference gives the immune system a chance to deal with the infection without having to circumnavigate its virulent attacks.
Choosing a genomic target
The FAST Platform uses bioinformatics to search through the microbial genome for a set of gene types, creating a library of potential PNA candidates that could deactivate the microbe. The system then searches through this PNA library and cross-checks it against the host DNA, eliminating any PNA candidates that are too similar to a host gene. This ensures that the PNA does not inadvertently block processes in the patient during treatment and generates highly specific PNAs that target only the pathogen of interest.
Synthesis & testing
Once the FAST software generates candidates for treatment of the pathogen, PNA synthesis machinery combines reagents in precise orders and quantities to create the intended PNA. Once it’s synthesized, it is extractedand tested in a Petri dish model of the infection. This model contains not only the pathogen of interest, but also host cells and non-pathogenic bacteria to ensure that the PNA targets only the pathogen causing the infection.
FAST PLATFORM THERAPEUTICS FOR COVID-19 TREATMENT
The FAST Platform is particularly well-suited to address COVID-19 infections. Previous work within the last 8 months has already characterized the genome of COVID-19, revealing numerous potential targets to deactivate the virus. Work is currently underway to test PNA targeting COVID-19 in animal models.
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Quantum dots are programmable, nanoparticle semiconductors that can kill a wide range of multidrug-resistant becterial clinical isolates. The killing effect is independent of material and controlled by the redox potentials of the photo-generated charge carriers, which selectively alter the cellular redox state. Given the rapid design build, and test cycle, we are exploring the safety and efficacy of Quantum Dot Antibiotics in pre-clinical studies. Photoexcited Quantum Dots could be used in the study of the effects of redox states on living systems and lead to clinical phototherapy for treatment of infections.
Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of traditional, small-molecule antibiotics. As bacteria develop new ways to resist our established approaches, we're losing the race in effective therapies for infectious disease.
We are exploring programmable, metal nanoparticle charge-carriers called quantum dots as a smart, tunable, alternative therapies for multidrug-resistant infections.
How quantum dots work
A property unique to atoms is their ability to be exited by very specific wavelengths of light. An excited atom jumps up to a higher energy level briefly before cascading back down to its base energy, releasing light or energy in its decent.
Metal nanoparticles release energy as they fall back down after being excited. This energy release has been shown to induce cell death, however, this attack is nonspecific and and surrounding tissue may suffer as well as pathogens.
Quantum dots are different because they are manufactured with extremely precise control over their energy fluctuations. We can activate quantum dots with light (photoexcitation) to make them release a controlled burst of energy as they relax back down to their normal state.
When your body's immune cells identify a foreign microbe or pathogen, a whole cascade of communication and coordinated action is initiated. Among these is the activation of phagocytes, specialized immune cells that engulf invaders and digest them in cellular contianers called lysosomes.
Conditions within lysosomes are brutal. They expose microbes to toxic chemicals while sequestering key resources that are necessary for survival. Several of the toxic chemicals are reactive oxygen species, highly reactive molecules that shred DNA and microbial components to eradicate engulfed pathogens.
The energy released by quantum dots generate reactive oxygen species that attack microbe the same way your immune system already does.
HARNESSING QUANTUM DOTS TO TREAT INFECTIOUS DISEASE
Several aspects of quantum dots make them particularly well-suited for treatment of bacterial infections. Their rapid and tunable synthesis enables response to new and emergent infections in real time. Once applied to a wound or infection, their small size allows them to readily diffuse into cells. Since we only need light to activate the quantum dots, we can use visible light for surface infections or infrared light for deep tissue infections, enabling controlled and localized treatment to prioritize patient health. Because quantum dots attack key processes and structures of microbes, they cannot evolve to resist quantum dot attack. Most importantly, quantum dots are safe. Experiments showed that quantum dots were able to clear intracellular infections without harming mammalian cells. The concentrations of Quantum Dot Antibiotics necessary to kill bacterial cells are harmless to our own human cells.
QUANTUM DOT ANTIBIOTICS IN THE ARC PIPELINE
Quantum dots have been proven capable of killing multidrug-resistant super bugs in vitro. Experiments testing Quantum Dot Antibiotics in pre-clinical animal models are currently underway, already revealing information about their safety and efficacy. Furthermore, Quantum Dot Antibiotics are being tested against biofilms, established microbial cities that afford them increased resilience against immune and antibiotic attack.
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Label-free MDR Pathogen Detection: We are developing optical techniques for molecular diagnostics or DNA sequencing to detect pathogens. Developing a label‐free optical DNA sequencing technique is based on nanoscale focusing of light, a high‐throughput and multiplexed identification method, and a data compression technique to rapidly identify sequences and analyze genomic heterogeneity for big datasets. Here, surface‐enhanced Raman spectroscopy is used to demonstrate label‐free identification of DNA nucleobases with multiplexed 3D plasmonic nanofocusing. While nanometer‐scale mode volumes prevent identification of single nucleobases within a DNA sequence, the block optical technique canidentify A, T, G, and C content in DNA k‐mers. These results pave the way for developing a novel, high‐throughput block optical sequencing method with lossy genomic data compression using k‐mer identification from multiplexed optical data acquisition.
Bacteria are constantly driven to adapt to new treatments, establishing a biological arms race between evolution and our ability to develop new antimicrobial treatments. As the balance of these processes has trended towards more resistance and fewer novel therapies, attention must be turned to new strategies which hinder the evolution of antibiotic resistance if the utility of our antibiotic arsenal is to be preserved. One such strategy involves manipulating the processes underpinning adaptation. To this end, we focus on controlling an integral element of evolutionary dynamics: negative epistasis. Negative epistasis describes the detrimental interactions between simultaneous mutations and is widely recognized to restrict adaptive pathways. However, such negative epistasis cannot be feasibly implemented as a therapeutic strategy, as this requires direct DNA manipulation. Manipulation of the transcriptome, conversely, is a much more tenable therapeutic path. This project offers a new paradigm by exploring “epigenetic epistasis” at the transcriptome level.