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Gene Delivery and Gene Editing (Focus Group - GDGE)

(191) VLP-mediated CRISPR/Cas9 gene editing of islets to inhibit IBMIR in islet transplantation

Introduction:

Instant blood-mediated inflammatory reaction (IBMIR) is a great hurdle in islet transplantation causing significant immediate graft loss post transplantation (1). IBMIR is primarily mediated by tissue factor (TF), which triggers the coagulation cascade leading to clot formation and plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis, causing ischemic injury in the graft (2, 3). Therefore, in this study, a virus-like particle (VLP) mediated CRISPR/Cas9 gene-editing strategy is utilized to knock out TF and PAI-1 genes in islets to reduce IBMIR and improve transplantation outcomes.

Learning Objectives:

  • Understand the role and impact of TF and PAI-1 in causing IBMIR in islet transplantation.
  • Evaluate the effectiveness of VLP-mediated CRISPR/Cas9 gene-editing strategy in islets.
  • Assess the effect of TF and PAI-1 deletions in reducing IBMIR and improving islet graft survival.