eVLP‐Mediated Cas9 Delivery for Preventing IBMIR in Islet Transplantation Article Swipe
Manju Shrestha
,
YeonJi Kim
,
Subin Park
,
Hu Lin Jiang
,
Jae Young Lee
,
Dae-Sik Kim
,
Jee-Heon Jeong
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/smll.202508128
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/smll.202508128
Islet transplantation is a promising strategy for effective β‐cell replacement in patients with type 1 diabetes. However, its success is hindered significantly by instant blood‐mediated inflammatory reaction (IBMIR), which leads to rapid graft loss. IBMIR is triggered when the transplanted islets come in contact with blood, activating the coagulation cascade, complement pathways, and innate immune responses. Tissue factor (TF), abundantly expressed on the islet surface, initiates the coagulation cascade, leading to thrombin formation, platelet activation, and neutrophil infiltration. Plasminogen activator inhibitor‐1 (PAI‐1) plays a critical role in IBMIR by inhibiting fibrinolysis and causing ischemic injury in the graft. TF and PAI‐1 contribute significantly to IBMIR, thus making them critical targets for genetic interventions to prevent IBMIR. In this study, an engineered virus‐like particle (eVLP)–mediated Cas9 nuclease is employed to knock out TF and PAI‐1 genes in rat islets. TF and PAI‐1 expression are effectively downregulated without inducing any off‐target effects or without compromising the viability and functionality of the islets. Streptozotocin‐induced diabetic mice transplanted with TF ‐ and PAI‐1 ‐knockout islets exhibited improved glycemic control and a significant reduction in the plasma levels of thrombin‐antithrombin (TAT) complex and complement component 3a (C3a), indicating the successful inhibition of IBMIR post‐transplantation.
Related Topics
Concepts
Islet
Transplantation
Fibrinolysis
Complement system
Innate immune system
Inflammation
Immunology
Medicine
Immune system
Tissue factor
Coagulation
Thrombin
Glycemic
Plasminogen activator
Cancer research
Tissue plasminogen activator
Platelet
Biology
Activator (genetics)
Cas9
Plasminogen activator inhibitor-1
TLR4
Proinflammatory cytokine
Xenotransplantation
Fibrin
Nuclease
Ischemia
Cell biology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/smll.202508128
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/smll.202508128
- OA Status
- hybrid
- References
- 54
- OpenAlex ID
- https://openalex.org/W7105899156
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7105899156Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/smll.202508128Digital Object Identifier
- Title
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eVLP‐Mediated Cas9 Delivery for Preventing IBMIR in Islet TransplantationWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-11-18Full publication date if available
- Authors
-
Manju Shrestha, YeonJi Kim, Subin Park, Hu Lin Jiang, Jae Young Lee, Dae-Sik Kim, Jee-Heon JeongList of authors in order
- Landing page
-
https://doi.org/10.1002/smll.202508128Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/smll.202508128Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/smll.202508128Direct OA link when available
- Concepts
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Islet, Transplantation, Fibrinolysis, Complement system, Innate immune system, Inflammation, Immunology, Medicine, Immune system, Tissue factor, Coagulation, Thrombin, Glycemic, Plasminogen activator, Cancer research, Tissue plasminogen activator, Platelet, Biology, Activator (genetics), Cas9, Plasminogen activator inhibitor-1, TLR4, Proinflammatory cytokine, Xenotransplantation, Fibrin, Nuclease, Ischemia, Cell biologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
-
54Number of works referenced by this work
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