Limitations of conventional delivery methods for miRNA therapeutics in neurological disorders
Limitation
Description
Reference
BBB impedance
The BBB restricts the passage of most therapeutic agents, including miRNAs, due to its selective nature and the hydrophilic, charged characteristics of miRNAs.
Efficient cellular uptake of miRNAs into specific target cells in the brain is challenging due to the complex internalization mechanisms of neurons and glial cells.
Systemically administered miRNAs may be rapidly cleared from the bloodstream and degraded by nucleases, reducing their bioavailability and therapeutic efficacy.
miRNAs are susceptible to degradation in biological fluids, necessitating protection from enzymatic degradation to maintain therapeutic levels at the target site.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Schickel R, Boyerinas B, Park S, Peter ME. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death.Oncogene. 2008;27:5959–74. [DOI] [PubMed]
Cao D, Li L, Chan W. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases.Int J Mol Sci. 2016;17:842. [DOI] [PubMed] [PMC]
DeVeale B, Swindlehurst-Chan J, Blelloch R. The roles of microRNAs in mouse development.Nat Rev Genet. 2021;22:307–23. [DOI] [PubMed]
Tan L, Yu J, Tan L. Causes and Consequences of MicroRNA Dysregulation in Neurodegenerative Diseases.Mol Neurobiol. 2015;51:1249–62. [DOI] [PubMed]
McKeever PM, Schneider R, Taghdiri F, Weichert A, Multani N, Brown RA, et al. MicroRNA expression levels are altered in the cerebrospinal fluid of patients with young-onset Alzheimer’s disease.Mol Neurobiol. 2018;55:8826–41. [DOI] [PubMed] [PMC]
Thangavelu L, Moglad E, Afzal M, Almalki WH, Malathi H, Bansal P, et al. Non-coding RNAs in Parkinson’s disease: Regulating SNCA and alpha-synuclein aggregation.Pathol Res Pract. 2024;261:155511. [DOI] [PubMed]
García-Fonseca Á, Martin-Jimenez C, Barreto GE, Pachón AFA, González J. The emerging role of long non-coding RNAs and microRNAs in neurodegenerative diseases: a perspective of machine learning.Biomolecules. 2021;11:1132. [DOI] [PubMed] [PMC]
Silvestro S, Mazzon E. MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury.Cells. 2022;11:2177. [DOI] [PubMed] [PMC]
Ye Y, Xu H, Su X, He X. Role of MicroRNA in Governing Synaptic Plasticity.Neural Plast. 2016;2016:4959523. [DOI] [PubMed] [PMC]
Yoshino Y, Roy B, Dwivedi Y. Differential and unique patterns of synaptic miRNA expression in dorsolateral prefrontal cortex of depressed subjects.Neuropsychopharmacology. 2021;46:900–10. [DOI] [PubMed] [PMC]
Hu Z, Li Z. miRNAs in synapse development and synaptic plasticity.Curr Opin Neurobiol. 2017;45:24–31. [DOI] [PubMed] [PMC]
Rago L, Beattie R, Taylor V, Winter J. miR379-410 cluster miRNAs regulate neurogenesis and neuronal migration by fine-tuning N-cadherin.EMBO J. 2014;33:906–20. [DOI] [PubMed] [PMC]
Ge X, Guo M, Hu T, Li W, Huang S, Yin Z, et al. Increased Microglial Exosomal miR-124-3p Alleviates Neurodegeneration and Improves Cognitive Outcome after rmTBI.Mol Ther. 2020;28:503–22. [DOI] [PubMed] [PMC]
Kang Q, Xiang Y, Li D, Liang J, Zhang X, Zhou F, et al. MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells.Oncotarget. 2017;8:24314–26. [DOI] [PubMed] [PMC]
Miyazaki Y, Adachi H, Katsuno M, Minamiyama M, Jiang Y, Huang Z, et al. Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF2.Nat Med. 2012;18:1136–41. [DOI] [PubMed]
Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia.Mol Ther Nucleic Acids. 2017;7:278–87. [DOI] [PubMed] [PMC]
Nguyen HD, Kim M. Exposure to a mixture of heavy metals induces cognitive impairment: Genes and microRNAs involved.Toxicology. 2022;471:153164. [DOI] [PubMed]
Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, et al. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes.Cancer Res. 2009;69:7569–76. [DOI] [PubMed] [PMC]
Fukuoka M, Takahashi M, Fujita H, Chiyo T, Popiel HA, Watanabe S, et al. Supplemental Treatment for Huntington’s Disease with miR-132 that Is Deficient in Huntington’s Disease Brain.Mol Ther Nucleic Acids. 2018;11:79–90. [DOI] [PubMed] [PMC]
Mei Z, Liu J, Schroeder JP, Weinshenker D, Duong DM, Seyfried NT, et al. Lowering Hippocampal miR-29a Expression Slows Cognitive Decline and Reduces Beta-Amyloid Deposition in 5×FAD Mice.Mol Neurobiol. 2024;61:3343–56. [DOI] [PubMed] [PMC]
Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, et al. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1.J Neurosci. 2008;28:1213–23. [DOI] [PubMed] [PMC]
Yang Y, Ye Y, Fan K, Luo J, Yang Y, Ma Y. MiR-124 reduced neuroinflammation after traumatic brain injury by inhibiting TRAF6.Neuroimmunomodulation. 2023;30:55–68. [DOI] [PubMed] [PMC]
Estrada-Meza C, Torres-Copado A, González-Melgoza LL, Ruiz-Manriquez LM, Donato MD, Sharma A, et al. Recent insights into the microRNA and long non-coding RNA-mediated regulation of stem cell populations.3 Biotech. 2022;12:270. [DOI] [PubMed] [PMC]
Ying S, Chang DC, Lin S. The microRNA (miRNA): overview of the RNA genes that modulate gene function.Mol Biotechnol. 2008;38:257–68. [DOI] [PubMed] [PMC]
Bofill-De Ros X, Vang Ørom UA. Recent progress in miRNA biogenesis and decay.RNA Biol. 2024;21:1–8. [DOI] [PubMed] [PMC]
Paturi S, Deshmukh MV. A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective.Front Mol Biosci. 2021;8:643657. [DOI] [PubMed] [PMC]
Kapplingattu SV, Bhattacharya S, Adlakha YK. MiRNAs as major players in brain health and disease: current knowledge and future perspectives.Cell Death Discov. 2025;11:7. [DOI] [PubMed] [PMC]
Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions.Int J Mol Sci. 2016;17:1712. [DOI] [PubMed] [PMC]
George TP, Subramanian S, Supriya MH. A brief review of noncoding RNA.Egypt J Med Hum Genet. 2024;25:98. [DOI]
Mirzaei H, Rahimian N, Mirzaei HR, Nahand JS, Hamblin MR. MicroRNAs in cancer.In: Exosomes and MicroRNAs in biomedical science. Cham: Springer; 2022. pp. 11–40. [DOI]
Yoshida T, Asano Y, Ui-Tei K. Modulation of MicroRNA Processing by Dicer via Its Associated dsRNA Binding Proteins.Noncoding RNA. 2021;7:57. [DOI] [PubMed] [PMC]
Nogami M, Miyamoto K, Hayakawa-Yano Y, Nakanishi A, Yano M, Okano H. DGCR8-dependent efficient pri-miRNA processing of human pri-miR-9-2.J Biol Chem. 2021;296:100409. [DOI] [PubMed] [PMC]
Ergin K, Çetinkaya R. Regulation of MicroRNAs.Methods Mol Biol. 2022;2257:1–32. [DOI] [PubMed]
Kim H, Lee Y, Kim VN. The biogenesis and regulation of animal microRNAs.Nat Rev Mol Cell Biol. 2025;26:276–96. [DOI] [PubMed]
Köhler A, Hurt E. Exporting RNA from the nucleus to the cytoplasm.Nat Rev Mol Cell Biol. 2007;8:761–73. [DOI] [PubMed]
Jodder J. Regulation of pri-MIRNA processing: mechanistic insights into the miRNA homeostasis in plant.Plant Cell Rep. 2021;40:783–98. [DOI] [PubMed]
Hynes C, Kakumani PK. Regulatory role of RNA-binding proteins in microRNA biogenesis.Front Mol Biosci. 2024;11:1374843. [DOI] [PubMed] [PMC]
Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA.Nature. 2004;431:343–9. [DOI] [PubMed]
Leitão AL, Enguita FJ. A Structural View of miRNA Biogenesis and Function.Noncoding RNA. 2022;8:10. [DOI] [PubMed] [PMC]
Masliah G, Maris C, König SL, Yulikov M, Aeschimann F, Malinowska AL, et al. Structural basis of siRNA recognition by TRBP double-stranded RNA binding domains.EMBO J. 2018;37:e97089. [DOI] [PubMed] [PMC]
Iwakawa H, Tomari Y. Life of RISC: Formation, action, and degradation of RNA-induced silencing complex.Mol Cell. 2022;82:30–43. [DOI] [PubMed]
Roy B, Lee E, Li T, Rampersaud M. Role of miRNAs in Neurodegeneration: From Disease Cause to Tools of Biomarker Discovery and Therapeutics.Genes (Basel). 2022;13:425. [DOI] [PubMed] [PMC]
Bhatti GK, Khullar N, Sidhu IS, Navik US, Reddy AP, Reddy PH, et al. Emerging role of non-coding RNA in health and disease.Metab Brain Dis. 2021;36:1119–34. [DOI] [PubMed] [PMC]
Navickas A, Asgharian H, Winkler J, Fish L, Garcia K, Markett D, et al. An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus.Nat Cell Biol. 2023;25:892–903. [DOI] [PubMed] [PMC]
Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways.Nat Rev Mol Cell Biol. 2019;20:5–20. [DOI] [PubMed]
Ali A, Khatoon A, Shao C, Murtaza B, Tanveer Q, Su Z. Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention.RNA Biol. 2024;21:1–18. [DOI] [PubMed] [PMC]
Menon A, Abd-Aziz N, Khalid K, Poh CL, Naidu R. miRNA: A Promising Therapeutic Target in Cancer.Int J Mol Sci. 2022;23:11502. [DOI] [PubMed] [PMC]
Alkhazaali-Ali Z, Sahab-Negah S, Boroumand AR, Tavakol-Afshari J. MicroRNA (miRNA) as a biomarker for diagnosis, prognosis, and therapeutics molecules in neurodegenerative disease.Biomed Pharmacother. 2024;177:116899. [DOI] [PubMed]
Abubakar M, Hajjaj M, Naqvi ZEZ, Shanawaz H, Naeem A, Padakanti SSN, et al. Non-Coding RNA-Mediated Gene Regulation in Cardiovascular Disorders: Current Insights and Future Directions.J Cardiovasc Transl Res. 2024;17:739–67. [DOI] [PubMed]
Dalal S, Ramirez-Gomez J, Sharma B, Devara D, Kumar S. MicroRNAs and synapse turnover in Alzheimer’s disease.Ageing Res Rev. 2024;99:102377. [DOI] [PubMed]
Ma ZX, Liu Z, Xiong HH, Zhou ZP, Ouyang LS, Xie FK, et al. MicroRNAs: protective regulators for neuron growth and development.Neural Regen Res. 2023;18:734–45. [DOI] [PubMed] [PMC]
Dawar P, Adhikari I, Mandal SN, Jayee B. RNA Metabolism and the Role of Small RNAs in Regulating Multiple Aspects of RNA Metabolism.Noncoding RNA. 2024;11:1. [DOI] [PubMed] [PMC]
Ismail NH, Mussa A, Al-Khreisat MJ, Yusoff SM, Husin A, Al-Jamal HAN, et al. Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma.Noncoding RNA. 2023;9:68. [DOI] [PubMed] [PMC]
Sharma M, Tanwar AK, Purohit PK, Pal P, Kumar D, Vaidya S, et al. Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer’s disease pathogenesis.Neurosci Biobehav Rev. 2024;161:105685. [DOI] [PubMed]
Tryphena KP, Anuradha U, Kumar R, Rajan S, Srivastava S, Singh SB, et al. Understanding the Involvement of microRNAs in Mitochondrial Dysfunction and Their Role as Potential Biomarkers and Therapeutic Targets in Parkinson’s Disease.J Alzheimers Dis. 2023;94:S187–202. [DOI] [PubMed] [PMC]
Zhang M, Bian Z. Alzheimer’s Disease and microRNA-132: A Widespread Pathological Factor and Potential Therapeutic Target.Front Neurosci. 2021;15:687973. [DOI] [PubMed] [PMC]
Li Y, Yu C, Jiang X, Fu J, Sun N, Zhang D. The mechanistic view of non-coding RNAs as a regulator of inflammatory pathogenesis of Parkinson’s disease.Pathol Res Pract. 2024;258:155349. [DOI] [PubMed]
Laneve P, Tollis P, Caffarelli E. RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.Int J Mol Sci. 2021;22:10285. [DOI] [PubMed] [PMC]
Bai Y, Su X, Piao L, Jin Z, Jin R. Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential.Front Mol Neurosci. 2021;14:556215. [DOI] [PubMed] [PMC]
Ma YM, Zhao L. Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases.Behav Neurol. 2023;2023:8537296. [DOI] [PubMed] [PMC]
Zhao X, Chen X, Wu X, Zhu L, Long J, Su L, et al. Machine Learning Analysis of MicroRNA Expression Data Reveals Novel Diagnostic Biomarker for Ischemic Stroke.J Stroke Cerebrovasc Dis. 2021;30:105825. [DOI] [PubMed]
Al-Jehani HM, Mousa AH, Alhamid MA, Al-Mufti F. Role of microRNA in the risk stratification of ischemic strokes.Front Neurol. 2025;16:1499493. [DOI] [PubMed] [PMC]
Su J, Song Y, Zhu Z, Huang X, Fan J, Qiao J, et al. Cell-cell communication: new insights and clinical implications.Signal Transduct Target Ther. 2024;9:196. [DOI] [PubMed] [PMC]
Hossain MM, Khan N, Sultana A, Ma P, McKyer ELJ, Ahmed HU, et al. Prevalence of comorbid psychiatric disorders among people with autism spectrum disorder: An umbrella review of systematic reviews and meta-analyses.Psychiatry Res. 2020;287:112922. [DOI] [PubMed]
Mohammadi AH, Seyedmoalemi S, Moghanlou M, Akhlagh SA, Zavareh SAT, Hamblin MR, et al. MicroRNAs and Synaptic Plasticity: From Their Molecular Roles to Response to Therapy.Mol Neurobiol. 2022;59:5084–102. [DOI] [PubMed]
Tsermpini EE, Kalogirou CI, Kyriakopoulos GC, Patrinos GP, Stathopoulos C. miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders.Pharmacogenomics J. 2022;22:211–22. [DOI] [PubMed]
Brum CB, Paixão-Côrtes VR, Carvalho AM, Martins-Silva T, Carpena MX, Ulguim KF, et al. Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility.World J Biol Psychiatry. 2021;22:456–67. [DOI] [PubMed]
Ilieva MS. Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis.Cells. 2024;13:1063. [DOI] [PubMed] [PMC]
Fišar Z. Biological hypotheses, risk factors, and biomarkers of schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry. 2023;120:110626. [DOI] [PubMed]
Musazzi L, Mingardi J, Ieraci A, Barbon A, Popoli M. Stress, microRNAs, and stress-related psychiatric disorders: an overview.Mol Psychiatry. 2023;28:4977–94. [DOI] [PubMed]
Hicks SD, Middleton FA. A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.Front Psychiatry. 2016;7:176. [DOI] [PubMed] [PMC]
Garcia G, Pinto S, Ferreira S, Lopes D, Serrador MJ, Fernandes A, et al. Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease.Cells. 2022;11:3377. [DOI] [PubMed] [PMC]
Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, et al. MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer’s disease.EMBO J. 2014;33:1667–80. [DOI] [PubMed] [PMC]
Puranik N, Song M. Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer’s Disease.Int J Mol Sci. 2024;25:9936. [DOI] [PubMed] [PMC]
Liu J, Zuo X, Han J, Dai Q, Xu H, Liu Y, et al. MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3β.Biosci Biotechnol Biochem. 2020;84:2273–80. [DOI] [PubMed]
Zhang X, Yang R, Hu B, Lu P, Zhou L, He Z, et al. Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson’s Disease.Front Cell Neurosci. 2017;11:170. [DOI] [PubMed] [PMC]
Zhang L, Wang M, Yang H, Tian T, Sun G, Ji Y, et al. Dopaminergic neuron injury in Parkinson’s disease is mitigated by interfering lncRNA SNHG14 expression to regulate the miR-133b/ α-synuclein pathway.Aging (Albany NY). 2019;11:9264–79. [DOI] [PubMed] [PMC]
Li N, Pan X, Zhang J, Ma A, Yang S, Ma J, et al. Plasma levels of miR-137 and miR-124 are associated with Parkinson’s disease but not with Parkinson’s disease with depression.Neurol Sci. 2017;38:761–7. [DOI] [PubMed]
Miñones-Moyano E, Porta S, Escaramís G, Rabionet R, Iraola S, Kagerbauer B, et al. MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function.Hum Mol Genet. 2011;20:3067–78. [DOI] [PubMed]
Chen Q, Deng N, Lu K, Liao Q, Long X, Gou D, et al. Elevated plasma miR-133b and miR-221-3p as biomarkers for early Parkinson’s disease.Sci Rep. 2021;11:15268. [DOI] [PubMed] [PMC]
Kramer S, Haghikia A, Bang C, Scherf K, Pfanne A, Duscha A, et al. Elevated levels of miR-181c and miR-633 in the CSF of patients with MS: A validation study.Neurol Neuroimmunol Neuroinflamm. 2019;6:e623. [DOI] [PubMed] [PMC]
Haghikia A, Haghikia A, Hellwig K, Baraniskin A, Holzmann A, Décard BF, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study.Neurology. 2012;79:2166–70. [DOI] [PubMed]
Sharaf-Eldin WE, Kishk NA, Gad YZ, Hassan H, Ali MAM, Zaki MS, et al. Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases.J Neurol Sci. 2017;383:188–98. [DOI] [PubMed]
Freischmidt A, Müller K, Ludolph AC, Weishaupt JH. Systemic dysregulation of TDP-43 binding microRNAs in amyotrophic lateral sclerosis.Acta Neuropathol Commun. 2013;1:42. [DOI] [PubMed] [PMC]
Cunha C, Santos C, Gomes C, Fernandes A, Correia AM, Sebastião AM, et al. Downregulated Glia Interplay and Increased miRNA-155 as Promising Markers to Track ALS at an Early Stage.Mol Neurobiol. 2018;55:4207–24. [DOI] [PubMed]
Gaughwin PM, Ciesla M, Lahiri N, Tabrizi SJ, Brundin P, Björkqvist M. Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington’s disease.Hum Mol Genet. 2011;20:2225–37. [DOI] [PubMed]
Hart M, Diener C, Lunkes L, Rheinheimer S, Krammes L, Keller A, et al. miR-34a-5p as molecular hub of pathomechanisms in Huntington’s disease.Mol Med. 2023;29:43. [DOI] [PubMed] [PMC]
Hoss AG, Labadorf A, Latourelle JC, Kartha VK, Hadzi TC, Gusella JF, et al. miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement.BMC Med Genomics. 2015;8:10. [DOI] [PubMed] [PMC]
Mao S, Wu J, Yan J, Zhang W, Zhu F. Dysregulation of miR-146a: a causative factor in epilepsy pathogenesis, diagnosis, and prognosis.Front Neurol. 2023;14:1094709. [DOI] [PubMed] [PMC]
Nomair AM, Mekky JF, El-Hamshary SA, Nomeir HM. Circulating miR-146a-5p and miR-132-3p as potential diagnostic biomarkers in epilepsy.Epilepsy Res. 2023;191:107089. [DOI] [PubMed]
Musso N, Bivona D, Bonomo C, Bonacci P, D’Ippolito ME, Boccagni C, et al. Investigating microRNAs as biomarkers in disorders of consciousness: a longitudinal multicenter study.Sci Rep. 2023;13:18415. [DOI] [PubMed] [PMC]
Jiménez-Morales JM, Hernández-Cuenca YE, Reyes-Abrahantes A, Ruiz-García H, Barajas-Olmos F, García-Ortiz H, et al. MicroRNA delivery systems in glioma therapy and perspectives: A systematic review.J Control Release. 2022;349:712–30. [DOI] [PubMed]
Sharma RK, Calderon C, Vivas-Mejia PE. Targeting Non-coding RNA for Glioblastoma Therapy: The Challenge of Overcomes the Blood-Brain Barrier.Front Med Technol. 2021;3:678593. [DOI] [PubMed] [PMC]
Zhang H, Vandesompele J, Braeckmans K, Smedt SCD, Remaut K. Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity.Chem Soc Rev. 2024;53:317–60. [DOI] [PubMed]
Bashyal S, Thapa C, Lee S. Recent progresses in exosome-based systems for targeted drug delivery to the brain.J Control Release. 2022;348:723–44. [DOI] [PubMed]
Kang H, Ga YJ, Kim SH, Cho YH, Kim JW, Kim C, et al. Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.J Biomed Sci. 2023;30:88. [DOI] [PubMed] [PMC]
Bulcha JT, Wang Y, Ma H, Tai PWL, Gao G. Viral vector platforms within the gene therapy landscape.Signal Transduct Target Ther. 2021;6:53. [DOI] [PubMed] [PMC]
Matsuzaka Y, Yashiro R. Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Curr Issues Mol Biol. 2024;46:8464–98. [DOI] [PubMed] [PMC]
Tseha ST. Role of Adenoviruses in Cancer Therapy.Front Oncol. 2022;12:772659. [DOI] [PubMed] [PMC]
Kordbacheh F, Farah CS. Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma.Cancers (Basel). 2021;13:5471. [DOI] [PubMed] [PMC]
Ma Y, Liao J, Cheng H, Yang Q, Yang H. Advanced gene therapy system for the treatment of solid tumour: A review.Mater Today Bio. 2024;27:101138. [DOI] [PubMed] [PMC]
Kotulska K, Fattal-Valevski A, Haberlova J. Recombinant Adeno-Associated Virus Serotype 9 Gene Therapy in Spinal Muscular Atrophy.Front Neurol. 2021;12:726468. [DOI] [PubMed] [PMC]
Arsenijevic Y, Berger A, Udry F, Kostic C. Lentiviral Vectors for Ocular Gene Therapy.Pharmaceutics. 2022;14:1605. [DOI] [PubMed] [PMC]
Xu C, Fang X, Xu X, Wei X. Genetic engineering drives the breakthrough of pig models in liver disease research.Liver Res. 2024;8:131–40. [DOI] [PubMed] [PMC]
Salarpour S, Barani M, Pardakhty A, Khatami M, Chauhan NP. The application of exosomes and exosome-nanoparticle in treating brain disorders.J Mol Liq. 2022;350:118549. [DOI]
Wu R, Gao W, Yao K, Ge J. Roles of Exosomes Derived From Immune Cells in Cardiovascular Diseases.Front Immunol. 2019;10:648. [DOI] [PubMed] [PMC]
Geng M, Chang Y, Li Z. Technologies for EV Surface Modification and its Application in Targeted Therapy. In: Li Z, editor. Extracellular Vesicle: Biology and Translational Application. Singapore: Springer; 2024. pp. 63–89. [DOI]
Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction.Elife. 2016;5:e19276. [DOI] [PubMed] [PMC]
Ghorai SM, Deep A, Magoo D, Gupta C, Gupta N. Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood-Brain Barrier (BBB).Pharmaceutics. 2023;15:1999. [DOI] [PubMed] [PMC]
Anwar S, Mir F, Yokota T. Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics. 2023;15:1130. [DOI] [PubMed] [PMC]
Lehto T, Kurrikoff K, Langel Ü. Cell-penetrating peptides for the delivery of nucleic acids.Expert Opin Drug Deliv. 2012;9:823–36. [DOI] [PubMed]
Naqvi AR, Fordham JB, Nares S. miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells.J Immunol. 2015;194:1916–27. [DOI] [PubMed] [PMC]
Verdera HC, Gitz-Francois JJ, Schiffelers RM, Vader P. Cellular uptake of extracellular vesicles is mediated by clathrin-independent endocytosis and macropinocytosis.J Control Release. 2017;266:100–8. [DOI] [PubMed]
Tian T, Zhu Y, Zhou Y, Liang G, Wang Y, Hu F, et al. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery.J Biol Chem. 2014;289:22258–67. [DOI] [PubMed] [PMC]
Sorets AG, Rosch JC, Duvall CL, Lippmann ES. Caveolae-Mediated Transport at the Injured Blood-Brain Barrier as an Underexplored Pathway for Central Nervous System Drug Delivery.Curr Opin Chem Eng. 2020;30:86–95. [DOI] [PubMed] [PMC]
Muqbil I, Bao B, Abou-Samra AB, Mohammad RM, Azmi AS. Nuclear export mediated regulation of microRNAs: potential target for drug intervention.Curr Drug Targets. 2013;14:1094–100. [DOI] [PubMed] [PMC]
Degors IMS, Wang C, Rehman ZU, Zuhorn IS. Carriers Break Barriers in Drug Delivery: Endocytosis and Endosomal Escape of Gene Delivery Vectors.Acc Chem Res. 2019;52:1750–60. [DOI] [PubMed] [PMC]
Bao QY, Geng DD, Xue JW, Zhou G, Gu SY, Ding Y, et al. Glutathione-mediated drug release from Tiopronin-conjugated gold nanoparticles for acute liver injury therapy.Int J Pharm. 2013;446:112–8. [DOI] [PubMed]
Chen CA, Zheng D, Xia Z, Shyu A. Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps.Nat Struct Mol Biol. 2009;16:1160–6. [DOI] [PubMed] [PMC]
Graczyk A, Radzikowska-Cieciura E, Kaczmarek R, Pawlowska R, Chworos A. Modified Nucleotides for Chemical and Enzymatic Synthesis of Therapeutic RNA.Curr Med Chem. 2023;30:1320–47. [DOI] [PubMed]
Yang S, Bögels BWA, Wang F, Xu C, Dou H, Mann S, et al. DNA as a universal chemical substrate for computing and data storage.Nat Rev Chem. 2024;8:179–94. [DOI] [PubMed]
Akyuz E, Aslan FS, Gokce E, Ilmaz O, Topcu F, Kakac S. Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease.Eur J Neurosci. 2024;60:6057–90. [DOI] [PubMed]
Azam HMH, Rößling RI, Geithe C, Khan MM, Dinter F, Hanack K, et al. MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Front Mol Neurosci. 2024;17:1386735. [DOI] [PubMed] [PMC]
Seyhan AA. Trials and Tribulations of MicroRNA Therapeutics.Int J Mol Sci. 2024;25:1469. [DOI] [PubMed] [PMC]
Choudhary A, Kumar A, Jindal M, Rhuthuparna M, Munshi A. MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.J Physiol Biochem. 2025;81:85–97. [DOI] [PubMed]
Zhang S, Cheng Z, Wang Y, Han T. The Risks of miRNA Therapeutics: In a Drug Target Perspective.Drug Des Devel Ther. 2021;15:721–33. [DOI] [PubMed] [PMC]
Reda El Sayed S, Cristante J, Guyon L, Denis J, Chabre O, Cherradi N. MicroRNA Therapeutics in Cancer: Current Advances and Challenges.Cancers (Basel). 2021;13:2680. [DOI] [PubMed] [PMC]
Rajanathadurai J, Perumal E, Sindya J. Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects.Funct Integr Genomics. 2024;24:164. [DOI] [PubMed]
Pei WD, Zhang Y, Yin TL, Yu Y. Epigenome editing by CRISPR/Cas9 in clinical settings: possibilities and challenges.Brief Funct Genomics. 2020;19:215–28. [DOI] [PubMed]
Lu D, Thum T. RNA-based diagnostic and therapeutic strategies for cardiovascular disease.Nat Rev Cardiol. 2019;16:661–74. [DOI] [PubMed]
Pinto-Hernandez P, Castilla-Silgado J, Coto-Vilcapoma A, Fernández-Sanjurjo M, Fernández-García B, Tomás-Zapico C, et al. Modulation of microRNAs through Lifestyle Changes in Alzheimer’s Disease.Nutrients. 2023;15:3688. [DOI] [PubMed] [PMC]
Braunger LJ, Knab F, Gasser T. Using Extracellular miRNA Signatures to Identify Patients with LRRK2-Related Parkinson’s Disease.J Parkinsons Dis. 2024;14:977–91. [DOI] [PubMed] [PMC]
