2. Academic Validation
  3. siRNA drug delivery across the blood-brain barrier in Alzheimer's disease

siRNA drug delivery across the blood-brain barrier in Alzheimer's disease

  • Adv Drug Deliv Rev. 2023 Aug:199:114968. doi: 10.1016/j.addr.2023.114968.
Muhammad Imran Sajid 1,  Fahad Sultan Sheikh 2,  Faiza Anis 3,  Nourina Nasim 4,  Rachita K Sumbria 5,  Surya M Nauli 6,  Rakesh Kumar Tiwari 7
Affiliations

Affiliations

  • 1 Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USA; Faculty of Pharmacy, University of Central Punjab, Lahore 54000, Pakistan.
  • 2 Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan.
  • 3 Department of Pharmacology, Faculty of Pharmaceutical Sciences, Federal Urdu University of Arts, Science and Technology, Karachi, Pakistan.
  • 4 Department of Chemistry and Chemical Engineering, Syed Baber Ali School of Science and Engineering, Lahore University of Management Sciences, 54792 Lahore, Pakistan.
  • 5 Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USA; Department of Neurology, University of California, Irvine, CA, 92868, USA.
  • 6 Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USA.
  • 7 Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University School of Pharmacy, Irvine, CA 92618, USA. Electronic address: tiwari@chapman.edu.
PMID: 37353152 DOI: 10.1016/j.addr.2023.114968
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed. We comprehensively report the latest advances in AD pathophysiology, druggable targets, ongoing clinical trials, and the siRNA-based approaches across the blood-brain barrier for addressing AD. This review describes the latest delivery systems employed to address this barrier. Critical insights and future perspectives on siRNA therapy for AD are also provided.

Keywords

AD models; Alzheimer's disease; Coding genes; Gene Silencing; Mitigation strategies; Non-coding sequences; RNAi; Target genes; siRNA therapeutics.

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