Objective
The objective of this project is to investigate the potential of specialized lipid nanoparticles (LNPs) to selectively target insulin-secreting β-cells and deliver therapeutic agents to these cells, with the aim of delaying or preventing Type 1 Diabetes (T1D). Given the limited efficacy of immune-targeted therapies, this research shifts focus towards treatment of the β-cells, which are known key contributors to T1D progression. The project proposes two aims: firstly, to establish the targeting specificity of LNPs for both mouse and human β-cells to ensure minimal impact on other cell types; and secondly, to investigate the role of one protein, PD-L1, in β-cells as a potential therapeutic agent. The project involves using specialized LNPs to deliver PD-L1 mRNA, to evaluate the impact on β-cell health and diabetes incidence in T1D mouse model. By advancing β-cell-centric therapies and improving targeting precision, this project aims to complement existing immunotherapies, reduce off-target effects, and deepen understanding of β-cell involvement in disease pathogenesis. This project seeks to potentially develop an innovative therapeutic approach to tackle T1D.
Background Rationale
Type 1 diabetes (T1D) research has traditionally concentrated on how the immune system destroys the insulin-producing β-cells. While immune-targeted therapies have shown some success in preventing or slowing the disease, these treatments sometimes expose patients to serious and sometimes life-threatening infections. Furthermore, immune suppressing drugs treat patients once the disease has manifested and not during early stages of disease progression.
Recent studies suggest that β-cells themselves might contribute to the onset and progression of T1D. Previous work shows that these cells produce abnormal proteins that can subsequently trigger immune responses. This new perspective offers potential for developing β-cell-focused treatments. Such therapies could reduce stress on β-cells, preserve proper β-cell function, and potentially delay the onset of T1D with fewer side effects. One way to develop β-cell-focused therapy is by using tools that can specifically deliver drugs directly to β-cells.
Lipid nanoparticles (LNPs) have emerged as promising tools for targeted drug delivery. Successfully used in COVID-19 vaccines to deliver aid in the immune response, LNPs can carry various therapeutic materials and can be customized to target specific cells. While LNPs have been used to modulate immune responses and treat cancer, these tools have yet to be applied to target β-cells and defend against diabetes.
Description of Project
Type 1 diabetes (T1D) research has traditionally concentrated on how T-cells cause autoimmune reactions that destroy the insulin-producing β-cells. While immune-targeted therapies have shown some success in preventing or slowing the disease, these treatments sometimes expose patients to serious and sometimes life-threatening infections. Furthermore, immune suppressing drugs treat patients once the disease has manifested and not during early stages of disease progression. Other therapies must be developed to not only treat patients for prevention, but also to improve quality of care.
Recent studies suggest that β-cells themselves might contribute to the onset and progression of T1D. These cells may produce abnormal proteins that can trigger immune responses. This new perspective offers potential for developing β-cell-focused treatments. Such therapies could help reduce immune stress on β-cells, preserve proper β-cell function, and potentially delay the onset of T1D with fewer side effects. One way to develop β-cell-focused therapy is by using tools that can specifically deliver drugs directly to β-cells.
Lipid nanoparticles (LNPs) have emerged as promising tools for targeted drug delivery. Successfully used in COVID-19 vaccines to deliver immune-informing agents, LNPs can carry various therapeutic materials (like mRNA or other beneficial proteins) and be customized to target specific cell types. While LNPs have been previously used to modulate immune responses and treat cancer, these tools have yet to be applied to target β-cells in diabetes.
This research proposes using specialized LNPs to target β-cells specifically and deliver therapeutic agents that could alter the progression of T1D.
Anticipated Outcome
Our preliminary research suggests that development of targeted β-cell therapies will be translated from mouse models into human model systems. We anticipate that this work will not only increase our scientific knowledge about β-cells during T1D, but also generate therapies that can prevent or delay disease progression. Furthermore, we anticipate that this work will also contribute towards another tool for fellow scientists and physicians to use in the fight against T1D.
Relevance to T1D
While immune-targeted therapies have shown some success in preventing or slowing the disease, these treatments sometimes expose patients to serious and sometimes life-threatening infections. Furthermore, immune suppressing drugs treat patients once the disease has manifested and not during early stages of disease progression.
Given the limited efficacy of immune-targeted therapies, my proposed research shifts focus towards treatment of the β-cells. Recent studies suggest that β-cells themselves might contribute to the onset and progression of T1D. This new perspective offers potential for developing β-cell-focused treatments before disease manifestation. By advancing β-cell-centric therapies and improving targeting precision, this project aims to complement existing immunotherapies, reduce off-target effects, and deepen understanding of β-cell involvement in T1D pathogenesis.