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NIH Funding Engineered Phage Screening Device

Scanning electron microscope image of bacteriophages (AFADadcADSasd, Wikimedia Commons)

15 July 2022. National Institutes of Health is funding initial development of a microfluidic device that tests engineered viruses for their ability to kill disease-causing bacteria. Felix Biotechnology Inc. in San Francisco is receiving a $314,400 award from National Institute of General Medical Sciences or NIGMS for the one-year project.

Felix Bio designs synthetic bacteriophage viruses, natural enemies of bacteria, particularly for attacking bacteria becoming resistant to today’s antibiotics. Bacteriophages, or phages, infect and replicate inside bacteria, where the viruses produce lysin enzymes that break down the bacterial cell walls, destroying the bacteria. The company says it uses machine learning algorithms to find genetic underpinnings for a range of bacteria, and design synthetic phages that attack those targets.

In their natural state, phages attack specific bacteria, not various types of microbes, and host bacteria can become resistant to phages. As a result, says Felix Bio, phages in nature are effective against only a limited number of microbes. In the NIGMS project, the company proposes creating a microfluidic device, also known as a lab-on-a-chip, that can screen engineered phages for their anti-bacterial capability to identify candidates for new antibiotics.

For the project, Felix Bio is enlisting the aid of biomedical engineering professor Adam Abate at University of California in San Francisco. Abate’s lab studies microfluidics and computer science applied to cell and microbiology, including techniques for assessing genomic activities of individual cells with tiny fluid droplets. The lab also investigates the use of unique identifiers acting like bar codes in genomic assemblies for synthetic biology, techniques demonstrated in a paper published earlier this year.

Tag phages with unique nucleic acid identifiers

Abate says microfluidics for genomic analysis and assembly also make possible harnessing advanced computational techniques like artificial intelligence to engineer phage viruses. “With microfluidics,” says Abate in a Felix Bio statement released through Cision, “we can generate the large amount of data needed to leverage the power of machine learning approaches to identify how to engineer viruses to kill a broader range of bacteria.”

The NIGMS project calls for a Felix Bio team to uniquely tag phages with identifiers made of single nucleic acid strands in droplets that flow through microfluidic channels. The team will merge the droplets to assemble phage components into engineered phages and sequence the synthetic phages for their ability to produce lysin enzymes for their antimicrobial properties against specified bacteria. Researchers will then assess the microfluidic system with a matrix of 10 phages and 10 bacteria, and validate the findings against conventional measurement systems.

“Phage therapy has been around for a long time,” notes Felix Bio CEO Robert McBride, also principle investigator on the project, “but has not reached its potential due to the narrow host ranges of most therapeutic phages. The tools being developed in this grant will allow us to overcome this key technical limitation and develop generalizable phage therapy to effectively treat antimicrobial resistant infections and save lives.”

The award is a Small Business Innovation Research or SBIR grant made under NIH’s small business programs that set aside a part of the agency’s research funding for U.S.-based and owned companies. Most SBIR grants are made in two parts: a first phase to determine technical and commercial feasibility, and a second phase to develop and test a working prototype or prepare for clinical trials. This is a first-phase project.

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