| First Author | Haroon MM | Year | 2019 |
| Journal | J Biosci | Volume | 44 |
| Issue | 1 | PubMed ID | 30837353 |
| Mgi Jnum | J:292991 | Mgi Id | MGI:6445072 |
| Citation | Haroon MM, et al. (2019) Delivery of BACE1 siRNA mediated by TARBP-BTP fusion protein reduces beta-amyloid deposits in a transgenic mouse model of Alzheimer's disease. J Biosci 44(1) |
| abstractText | Systemic delivery of nucleic acids to the central nervous system (CNS) is a major challenge for the development of RNA interference-based therapeutics due to lack of stability, target specificity, non-permeability to the blood-brain barrier (BBB), and lack of suitable carriers. Using a designed bi-functional fusion protein TARBP-BTP in a complex with siRNA, we earlier demonstrated knockdown of target genes in the brain of both AbetaPP-PS1 (Alzheimer's disease, AD) and wild-type C57BL/6 mice. In this report, we further substantiate the approach through an extended use in AbetaPP-PS1 mice, which upon treatment with seven doses of beta-secretase AbetaPP cleaving Enzyme 1 (BACE1) TARBP-BTP:siRNA, led to target-specific effect in the mouse brain. Concomitant gene silencing of BACE1, and consequent reduction in plaque load in the cerebral cortex and hippocampus (greater than 60%) in mice treated with TARBP-BTP:siRNA complex, led to improvement in spatial learning and memory. The study validates the efficiency of TARBP-BTP fusion protein as an efficient mediator of RNAi, giving considerable scope for future intervention in neurodegenerative disorders through the use of short nucleic acids as gene specific inhibitors. |
