Tag Archives: bioengineered diseases

How to Prepare for Deadly Flu and Nuclear Fallout

Breakthroughs in the science of programmable gene expression inspired DARPA to establish the PReemptive Expression of Protective Alleles and Response Elements (PREPARE) program with the goal of delivering powerful new defenses against public health and national security threats. DARPA has now selected five teams to develop a range of new medical interventions that temporarily and reversibly modulate the expression of protective genes to guard against acute threats from influenza and ionizing radiation, which could be encountered naturally, occupationally, or through a national security event.

The program builds from the understanding that the human body has innate defenses against many types of health threats, but that the body does not always activate these defenses quickly or robustly enough to block the worst damage. To augment existing physiological responses, PREPARE technologies would provide a programmable capability to up- or down-regulate gene expression on demand, providing timely, scalable defenses that are proportional to anticipated threats. Service members and first responders could administer these interventions prior to threat exposure or therapeutically after exposure to mitigate the risk of harm or death.

Influenza: “Researchers working within the PREPARE program seek to improve rates of survival and recovery in catastrophic scenarios for which reliable and scalable countermeasures don’t currently exist,” said Dr. Renee Wegrzyn, the PREPARE program manager….Three PREPARE teams are pursuing multi-pronged approaches to influenza defense and treatment that use programmable gene modulators to boost the human body’s natural defenses against influenza and also weaken the virus’ ability to cause harm by directly neutralizing the viral genomes. If successful, their approaches would potentially protect against virtually all influenza strains — regardless of whether a virus is newly emergent or has developed drug resistance — and would provide near instantaneous immunity, in contrast to traditional vaccines. Additionally, the teams are designing their countermeasures so that they are simple to deliver — for example, as intranasal sprays — reducing the logistical challenge of protecting large numbers of people.A team led by DNARx LLC, under principal investigator Dr. Robert Debs, aims to develop a new DNA-encoded gene therapy that helps patients fight influenza by boosting the natural immune response and other protective functions of their nasal passages and lungs.

Radiation Hazard Symbol

Ionizing Gamma Radiation: Other PREPARE teams are pursuing treatments to protect the body from the effects of ionizing gamma radiation. In humans, radiation poisoning primarily affects stem cells in the blood and gut, yet existing treatments only help to regenerate blood cells, and only with limited effect. There is no possibility for prophylactic administration of these drugs, and most must be delivered immediately following radiation exposure to provide any benefit. There are no existing medical countermeasures for radiation damage to the gut
A team led by the University of California, San Francisco, under principal investigator Dr. Jonathan Weissman, also aims to develop gene therapies to enhance resilience against ionizing radiation. The team’s approach should result in an intravenous or orally available treatment that activates innate defenses in gut and blood stem cells for a period of several weeks.

A Dose of Inner Strength to Survive and Recover from Potentially Lethal Health Threats
New tools for programmable modulation of gene expression could yield enhanced resilience against influenza and ionizing radiation for service members and first responders, DARPA Press Release, June 27, 2019

How to Kill Bacteria: Robo-Cells

Johns Hopkins University researchers are setting out to design and test self-directed microscopic warriors that can locate and neutralize dangerous strains of bacteria…[The goal] s to devise a prototype biocontrol system that can dispatch single-cell fighters to track down and engulf specific pathogens, rendering them harmless. The funding was awarded by the Defense Advanced Research Projects Agency, commonly called DARPA.

Possible first targets in this proof-of-concept project include Legionella, the bacteria that cause Legionnaire’s disease; and Pseudomonas aeruginosa, a bacterial strain that is the second-leading cause of infections found in hospitals. If the project succeeds, these tiny infection-fighters might one day be dispatched to curtail lethal microbes lurking in medical settings. Eventually, they could also be used to cleanse contaminated soil or possibly defend against bioterror attacks.

An important goal of the project is that each of the proposed soldier cells must carry out its own mission without relying on step-by-step commands from a remote human operator.

“Once you set up this biocontrol system inside a cell, it has to do its job autonomously, sort of like a self-driving car,” said Pablo A. Iglesias.”…In a similar way, the biocontrol systems we’re developing must be able to sense where the pathogens are, move their cells toward the bacterial targets, and then engulf them to prevent infections among people who might otherwise be exposed to the harmful microbes.”

These experts plan to biologically embed search-and-surround orders within a familiar type of amoeba cell called Dictyostelium discoideum [slime mold]. These widely studied microbes, commonly found in damp soil such as riverbeds, typically engulf and dine on bacteria, which are much smaller.  “These amoebas possess receptors that can detect the biochemical ‘scents’ emitted by bacteria,” Robinson said. “Our goal is to use concepts from control theory to design a ‘super amoeba’ that can recognize a particular bad guy—a specific type of disease-causing bacteria—and then move toward and attack these target cells.”  Robinson added: “The plan is to develop amoebas that are super-sensitive to these bacterial signals and home in on them as though they were a plate piled high with fresh chocolate chip cookies. The goal is to make these amoebas behave as though this is the most natural thing to do.”.. But if the project is successful, the researchers say the single-cell fighters could eventually be introduced into the cooling and ventilation system in a hospital, where they could feast on the bacteria that are currently causing dangerous infections. One possible method of introducing the infection fighters into such systems might be through use of a spray solution.

Iglesias noted that initial efforts will focus on bacteria lurking outside, not within the body.  “In this contract, we are not targeting bacteria in human blood,” he said, “but the hope is that the techniques we develop would ultimately be useful for that.”

Excerpts from Phil Sneiderman, Johns Hopkins researchers aim to design self-driving cells to pursue deadly bacteria, John Hopkins University, Feb. 2, 2016

On-Demand Germs: Bioengineering for the Military

From the DARPA websitThe development of increasingly sophisticated techniques and tools to sequence, synthesize and manipulate genetic material has led to the rapidly maturing discipline of synthetic biology. …[But] The costs of maintaining required environmental controls and detecting and compensating for genetic alterations are substantial and severely limit the widespread application of synthetic biology to U.S. national security missions.

To help address these challenges, DARPA has created the Biological Robustness in Complex Settings (BRICS)  BRICS seeks to develop the fundamental understanding and component technologies needed to increase the biological robustness and stability of engineered organisms while maintaining or enhancing the safe application of those organisms in complex biological environments. The goal is to create the technical foundation for future engineered biological systems to achieve greater biomedical, industrial and strategic potential.

“By making these systems more robust, stable and safe, BRICS seeks to harness the full range of capabilities at the intersection of engineering and biology,” said Justin Gallivan, DARPA program manager. “These capabilities could include efficient on-demand bio-production of novel drugs, fuels, sensors and coatings; or engineered microbes able to optimize human health by treating or preventing disease.”


Predator Bacteria for War

The  Pathogen Predators Program of DARPA would represent a significant departure from conventional antibacterial therapies that rely on small molecule antibiotics. While antibiotics have been remarkably effective in the past, their widespread use has led to the emergence of antibiotic-resistant bacterial infections that are difficult or impossible to treat. In vitro studies have shown that predators such as Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus can prey upon more than one hundred different human pathogens and will also prey on multi-drug resistant bacteria.

The Pathogen Predators program will answer three fundamental questions about bacterial predators:

1) Are predators toxic to recipient (host) organisms?
2) Against what pathogens (prey) are predators effective?
3) Can pathogens develop resistance to predation?

This list [of bacteria that could be killed by predator bacteria] includes NIAID (National Institute of Allergy and Infectious Diseases) Category A and B threats to national security:

NIAID Category A and B
Yersinia pestis (i.e. plague)
Francisella tularensis (i.e. tularemia)
Brucella species
Coxiella burnetii (i.e. Q fever)
Rickettsia prowazekii (i.e.  typhus)
Burkholderia mallei (i.e. glanders)
Burkholderia pseudomallei (i.e. melioidosis)

Source DARRA (pdf)