GLP-1 Phage Design

Abstract

Semaglutide-based pharmaceuticals have gained increasing interest in the clinical treatment of Type 2 Diabetes Mellitus (T2DM) due to their effectiveness in glycemic control. Acting as a glucagon-like peptide-1 receptor agonist (GLP-1RA), semaglutide enhances insulin secretion and promotes beta-cell survival. GLP-1RA therapeutics offer a promising alternative to insulin and existing treatments for the estimated 38 million Americans affected by diabetes, 90–95% of whom are classified as type 2. PhageCraft Therapeutics is proud to present our bacteriophage delivery system for in-situ GLP-1RA production.

Our system involves a single-infection phage designed to deliver and sustain GLP-1RA production using gut bacteria present in the distal ileum. By engineering bacteriophages to infect specific harmful bacteria, our flagship product enables localized, continuous in-situ production of a modified, more stable GLP-1RA. This approach minimizes patient involvement by eliminating injections and reduces systemic side effects seen with current GLP-1 therapeutics such as Ozempic.

The system begins with a genetic circuit that removes the viral capsid genes from bacteriophage DNA and inserts our modified GLP-1RA sequence. This modified DNA is combined with a helper plasmid containing the deleted capsid genes to produce phages independently of the capsid protein in their genome, resulting in phages that can replicate only once. These single-replication phages are then triple-encapsulated in a polymeric capsule.

Our engineered bacteriophages are enclosed in an enteric capsule made through a cost-effective, layer-by-layer process of film-coated alginate beads with alternating polyethylenimine and pectin layers. While there is a significant cost in purchasing custom nucleotide sequences for the high-accuracy custom oligonucleotide synthesis necessary for the genetic design of the bacteriophage, the associated gene sequences can be inserted into the bacteriophage plasmid containing the LacZ gene using the inexpensive PCR-based MEGAWHOP process.

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