CRISPR-modified cell lines for high-throughput SGLT1 and SGLT2 inhibitor screening

Overview

This research program delivers CRISPR-modified cell lines designed to accelerate the discovery and characterization of sodium-glucose cotransporter (SGLT1 and SGLT2) inhibitors. By using CRISPR technology to fluorescently label and knock out SGLT1 and SGLT2 in glucagon-secreting α-TC1 cells, the laboratory produces optimized screening tools that overcome the limitations of traditional overexpression-based assays. The resulting cell lines enable pharmaceutical and biotechnology partners to evaluate compound specificity, transporter localization, and glucose uptake inhibition with greater physiological relevance and throughput.

Technical specifications

Key features:

• CRISPR-based fluorescent tagging of endogenous SGLT1 and SGLT2 at the N- or C-terminus, preserving native expression regulation
• CRISPR knockout of SGLT1 and SGLT2 via stop codon insertion in exon 2, enabling clean loss-of-function studies
• High-throughput screening assay platform built on α-TC1 cells, which natively co-express SGLT1 and SGLT2
• Time-course expression and plasma membrane localization studies without artifacts from overexpression vectors
• Compound specificity assessment through comparative analysis in wild-type and knockout cell backgrounds
• Application to glucose uptake inhibitor discovery for metabolic disease drug development

Technology readiness level

The research is in the preclinical development stage with active laboratory validation underway. The team has established expertise in generating CRISPR-modified cell lines for gene function studies. Current objectives focus on confirming SGLT1 and SGLT2 protein expression in α-TC1 cells, generating fluorescently tagged and knockout variants, and validating the screening platform with known SGLT inhibitors. The platform is positioned for collaboration with pharmaceutical and biotechnology partners seeking improved cell-based assays for SGLT-targeted drug discovery.