4:17 PM
Oct 05, 2017
 |  BC Innovations  |  Product R&D

Avidly specific

How AvidBiotics is taking on the microbiome with bactericidal peptides.

With its first two programs headed for the clinic next year, AvidBiotics Corp. is seeing the fruits of its move to human therapeutics from food safety and animal health. Using engineered peptides, the company has built two platforms that give it plays in the ever-growing fields of the microbiome and CAR T cells.

The platforms, dubbed Avidocin and convertibleCAR, share few features, save the use of protein engineering to create compounds that aim to beat the competition on specificity and safety.

The bulk of AvidBiotics’ effort has gone to Avidocin, its flagship system for designing antimicrobial peptides to treat or prevent bacterial infections without harming the microbiome.

Last month in Science Translational Medicine, AvidBiotics published mechanistic data on a prototype Avidocin targeting Clostridium difficile. The paper showed the compound selectively killed specific strains, identified the bacterial target, and presented evidence of its low propensity to induce resistance.

Avidocins are engineered versions of R-type bacteriocins -- natural antimicrobial peptides secreted by bacteria to eliminate competing strains. The molecules are structured as contractile sheaths that inject their cores through the bacterial membrane of targeted strains specifically bound by the peptide's six tail fibers (see "Antimicrobial Avidity").

Figure: Antimicrobial avidity

After more than a decade of development, AvidBiotics Corp.’s Avidocin antimicrobial peptides are now nearing the clinic for prevention of bacterial infections. The peptides are engineered versions of natural bacteria-targeting bacteriocin peptides, re-targeted to kill therapeutically relevant bacterial strains.

An Avidocin is comprised of a long contractile sheath that injects its core into a specific bacteria targeted by receptor binding proteins attached near the peptide’s tail fibers.

AvidBiotic’s lead candidate, Avidocin-CD (yellow), was designed to bind multiple variants of Clostridium difficile surface layer protein A (C. difficile SlpA) (green) on the surface of most strains of the bacteria that cause disease in the U.S. When the Avidocin-CD attaches to the bacteria’s cell surface proteins, it injects its core through the cell membrane, creating a pore that dissipates membrane potential and immediately kills the cell. Source: AvidBiotics Corp.

While the mechanism resembles that of bacteriophages -- viruses that specifically infect bacteria -- the peptides cause a different pathology.

"Unlike bacteriophages that inject their DNA into target bacteria to ultimately kill the cell, bacteriocins don't inject anything. It's just a tube that pierces the membrane, but any molecules or atoms small enough can get...

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