Delivery of BACE1 siRNA mediated by TARBP-BTP fusion protein reduces β-amyloid deposits in a transgenic mouse model of Alzheimer’s disease View Full Text


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Article Info

DATE

2019-03

AUTHORS

Mohamed Mohamed Haroon, Kamal Saba, Venkata Harshavardhan Boddedda, Jerald Mahesh Kumar, Anant Bahadur Patel, Vijaya Gopal

ABSTRACT

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 AβPP-PS1 (Alzheimer's disease, AD) and wild-type C57BL/6 mice. In this report, we further substantiate the approach through an extended use in AβPP-PS1 mice, which upon treatment with seven doses of β-secretase AβPP 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. More... »

PAGES

1

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12038-018-9822-x

DOI

http://dx.doi.org/10.1007/s12038-018-9822-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111775630

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30837353


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