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Type 2 Diabetes (T2D) is characterized by chronic hyperglycemia and a significant loss of β-cell mass in pancreatic islets, leading to impaired insulin production and glucose regulation. Current treatments rely on exogenous insulin administration, which imposes substantial socioeconomic burdens and does not restore endogenous insulin secretion. Efforts to stimulate β-cell proliferation using small molecules have shown limited success due to non-selectivity and off-target effects. Gene therapy presents a promising alternative by delivering key transcription factors, such as Pancreatic And Duodenal Homeobox 1 (PDX1), to restore β-cell function and proliferation. However, existing viral vector technologies face significant challenges, including immunogenicity, complex engineering, and poor β-cell tropism. To overcome these limitations, we propose a novel bacteriophage-based gene delivery system utilizing the M13 phage to harbor PDX1 as its genetic cargo. To enhance β-cell specificity, we have engineered the phage to display glucagon-like peptide-1 (GLP-1) peptides on its gene product 3 region (tail fiber binding domain), facilitating targeted binding to β cells. This approach ensures selective delivery of PDX1, promoting β-cell regeneration while minimizing off-target effects. Our next steps include in vitro validation using various cell lines, including β cells and other pancreatic cell types, to confirm selective uptake and functional restoration. Additionally, we will assess the proliferation and insulin secretion of patient-derived pancreatic islets following treatment. If successful, this bacteriophage-based gene therapy could provide a targeted and cost-effective strategy to restore β-cell mass, offering a transformative advancement in T2D treatment.

Restoring pancreatic β-cell function with a next-generation chimeric bacteriophage viral vector

School

Dublin High School
Dublin, CA

BioBuilderClub Season

2024-2025 Season

Category

Resources

Abstract-DHS-BB

BioBuilder SlideshowPoster-Rruchir, Rayyan, Sid, Akshaj, Gurnoor, Diya, Rohith(USE)

DHS-BioBuilder – Akshaj and Rruchir

Dublin High School Team(Updated for use)

EDITED BBC Poster_Dublin High School_2025