Background: Recently, manipulation of gene expression and switching genes on or off highlights the potential of nucleic
acid-based therapies (NA-BTs). Alzheimer’s disease (AD) is a common devastating neurodegenerative disease (NDs) responsible for
60-80% of all cases of dementia and predicted that it will become a main public health concern among aged populations.
Objective: The aim of this study was to outline the current research in the field of NA-BTs for the treatment of AD disabilities, including strategies to suppress the memory and learning defects, to promote recovery processes, and to reinforce social relationships in
Method: This review was performed via evaluating PubMed reported studies from January 2010 to November 2019 also reference
lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies,
and controlled trials (CTs) on specific NA-BTs to AD were acceptable, although, in-vitro studies were excluded due to the considerable diversities and heterogeneities. After removing the duplicates according to preferred reporting items for systematic reviews and
meta-analyses (PRISMA) instruction, we merged remains titles across search databases.
Results: There are 40 ongoing studies related to the application of nucleic acids in the treatment and diagnosis of AD where the more
consideration is to DNA targeting strategies (12 targets for vectors and aptamers), antisense oligonucleotides (8 targets), micro-RNAs
mimics (7 targets), antagomiRs (6 targets), small interferences-RNAs (5 targets), as well as mRNAs (2 targets) respectively. All of
these targets are grouped into 4 categories according to their role in molecular pathways where amyloid-β (18 targets), neural survival (11 targets), memory and cognition (8 targets), and tau (3 targets) are more targeted pathways respectively.
Conclusion: With recent successes in the systemic delivery of nucleic acids via intravenous injection; it is worth investing in the production of new-generation medicines. There are still several challenges for NA-BTs including, their delivery to the effective modulators, mass production at low cost, sustaining efficacy and minimizing off‐target effects. Regarding miRNA-based therapies, given the
obvious involvement of miRNAs in numerous facets of brain disease, and the many sophisticated techniques for delivery to the brain,
miRNA-based therapies will make new hope for the treatment of neurological diseases such as AD.