Application of Brain-Targeted Anti-inflammatory RNA Nanoparticle for Ischemic Stroke Therapy

  • Haque, Farzin (PI)

Grants and Contracts Details


Although some of the cellular mechanisms of stroke development are fairly well understood, the neuronal death after ischemic stroke cannot be well controlled because of a lack of efficient treatments. The long-term goal of my research is to develop an effective strategy for ischemic stroke therapy. In the searching for new approaches for stroke therapy, I focus on targeting the post-ischemic inflammation at blood-brain barrier (BBB), because post-ischemic inflammation at the level of brain endothelium of the BBB plays an important role in pathology of ischemic stroke. We propose a novel solution in the proposal which is replacing the anti-ICAM-1 antibody with a RNA nanoparticle (named FRS-NP) consisting of anti-ICAM-1siRNA, packaging RNA (pRNA) of bacteriophage phi29, and a transferrin receptor (TfR) specific RNA aptamer (FB4). The pRNA is used as a vector to carry anti-ICAM-1 siRNA and FB4. The ligand targeting transport function and inhibitory function in ICAM-1 expression of FRS-NP are carried by FB4 and anti-iCAM-1siRNA, respectively. We will use the transient middle cerebral artery occlusion ischemic stroke model (tMCAO) as the brain ischemia/reperfusion (IR) injury model in vivo to demonstrate the feasibility of this vascular targeting strategy for treatment of ischemic stroke. The objective of this application is to develop a BBB targeted RNA complexes for therapy of ischemic stroke. Our central hypothesis is that the FRS-NPs have therapeutic effects on ischemic stroke by inhibition of post-ischemic inflammation. The expected outcomes of the proposed project are that FRS-NPs can be delivered into the brain endothelial cells at the BBB and exert an anti-inflammatory effect by inhibition of ICAM-1 expression, which leads to improvement of ischemic stroke outcomes. Targeting post-ischemic inflammation will give relatively longer therapeutic window, which is highly relevant to clinical application. If successful, it will explore a new therapeutic strategy for ischemic stroke, and this approach could be broadly applied for therapy of diseases affecting the BBB and the central nervous system (CNS).
Effective start/end date6/1/151/16/16


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.