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

Muhammad Imran Sajid; Fahad Sultan Sheikh; Faiza Anis; Nourina Nasim; Rachita K Sumbria; Surya M Nauli; Rakesh Kumar Tiwari

doi:10.1016/j.addr.2023.114968

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. Epub 2023 Jun 21.

Authors

Muhammad Imran Sajid¹, Fahad Sultan Sheikh², Faiza Anis³, Nourina Nasim⁴, Rachita K Sumbria⁵, Surya M Nauli⁶, Rakesh Kumar Tiwari⁷

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
PMCID: PMC10528676 (available on 2024-08-01)
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.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Blood-Brain Barrier
Drug Delivery Systems / methods
Humans
Neurodegenerative Diseases* / drug therapy
RNA, Small Interfering

Substances

RNA, Small Interfering

Abstract

Publication types

MeSH terms

Substances

Grants and funding