REFERENCES
1. Kim YK. RNA therapy: rich history, various applications and unlimited future prospects. Exp Mol Med. 2022;54:455-65.
2. Damase TR, Sukhovershin R, Boada C, Taraballi F, Pettigrew RI, Cooke JP. The limitless future of RNA therapeutics. Front Bioeng Biotechnol. 2021;9:628137.
3. Lam JK, Chow MY, Zhang Y, Leung SW. siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids. 2015;4:e252.
4. Hu B, Zhong L, Weng Y, et al. Therapeutic siRNA: state of the art. Signal Transduct Target Ther. 2020;5:101.
5. Fu Y, Chen J, Huang Z. Recent progress in microRNA-based delivery systems for the treatment of human disease. ExRNA. 2019;1:24.
6. Tang L, Chen HY, Hao NB, et al. MicroRNA inhibitors: natural and artificial sequestration of microRNA. Cancer Lett. 2017;407:139-47.
7. Mcdonald MK, Ajit SK. MicroRNA biology and pain. molecular and cell biology of pain. Elsevier; 2015. pp. 215-49.
8. Beavers KR, Nelson CE, Duvall CL. MiRNA inhibition in tissue engineering and regenerative medicine. Adv Drug Deliv Rev. 2015;88:123-37.
9. Yoo J, Hajjar RJ, Jeong D. Generation of efficient miRNA inhibitors using tough decoy constructs. In: Ishikawa K, Editor. Cardiac gene therapy. New York: Springer; 2017. pp. 41-53.
10. Chery J. RNA therapeutics: RNAi and antisense mechanisms and clinical applications. Postdoc J. 2016;4:35-50.
11. Zhu Y, Zhu L, Wang X, Jin H. RNA-based therapeutics: an overview and prospectus. Cell Death Dis. 2022;13:644.
13. Welsh JA, Goberdhan DCI, O’Driscoll L, et al; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404.
14. Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019;8:727.
15. Sharma V, Mukhopadhyay CD. Exosome as drug delivery system: current advancements. Extracell Vesicle. 2024;3:100032.
16. Amiri A, Bagherifar R, Ansari Dezfouli E, Kiaie SH, Jafari R, Ramezani R. Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications. J Transl Med. 2022;20:125.
17. Kim HI, Park J, Zhu Y, Wang X, Han Y, Zhang D. Recent advances in extracellular vesicles for therapeutic cargo delivery. Exp Mol Med. 2024;56:836-49.
18. Sen S, Xavier J, Kumar N, Ahmad MZ, Ranjan OP. Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives. 3 Biotech. 2023;13:101.
19. Jafari D, Shajari S, Jafari R, et al. Designer exosomes: a new platform for biotechnology therapeutics. BioDrugs. 2020;34:567-86.
20. Wang CK, Tsai TH, Lee CH. Regulation of exosomes as biologic medicines: regulatory challenges faced in exosome development and manufacturing processes. Clin Transl Sci. 2024;17:e13904.
21. Gupta D, Zickler AM, El Andaloussi S. Dosing extracellular vesicles. Adv Drug Deliv Rev. 2021;178:113961.
22. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341-5.
23. Xu L, Faruqu FN, Lim YM, et al. Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model after loco-regional treatment. Biomaterials. 2021;264:120369.
24. Zhang H, Yan W, Wang J, et al. Surface functionalization of exosomes for chondrocyte-targeted siRNA delivery and cartilage regeneration. J Control Release. 2024;369:493-505.
25. Zhang L, Liu M, Sun Q, et al. Engineering M2 type macrophage-derived exosomes for autoimmune hepatitis immunotherapy via loading siRIPK3. Biomed Pharmacother. 2024;171:116161.
26. Bai W, Zhu T, Zuo J, Li Y, Huang X, Li G. Delivery of SAV-siRNA via exosomes from adipose-derived stem cells for the treatment of myocardial infarction. Tissue Eng Regen Med. 2023;20:1063-77.
27. Cooper JM, Wiklander PB, Nordin JZ, et al. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov Disord. 2014;29:1476-85.
28. Rong Y, Wang Z, Tang P, et al. Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury. Bioact Mater. 2023;23:328-42.
29. Bai J, Duan J, Liu R, et al. Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells. Asian J Pharm Sci. 2020;15:461-71.
30. Zhang H, Wang Y, Bai M, et al. Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Sci. 2018;109:629-41.
31. Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546:498-503.
32. Greco KA, Franzen CA, Foreman KE, Flanigan RC, Kuo PC, Gupta GN. PLK-1 silencing in bladder cancer by siRNA delivered with exosomes. Urology. 2016;91:241.e1-7.
33. Liu Y, Li D, Liu Z, et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015;5:17543.
34. Han Q, Xie QR, Li F, et al. Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer. Theranostics. 2021;11:6526-41.
35. Pei X, Zhang X, Zhang L, et al. Targeted exosomes for co-delivery of siFGL1 and siTGF-β1 trigger combined cancer immunotherapy by remodeling immunosuppressive tumor microenvironment. Chem Eng J. 2021;421:129774.
36. Limoni SK, Moghadam MF, Moazzeni SM, Gomari H, Salimi F. Engineered exosomes for targeted transfer of siRNA to HER2 positive breast cancer cells. Appl Biochem Biotechnol. 2019;187:352-64.
37. Lu W, Zhang J, Wu Y, Sun W, Jiang Z, Luo X. Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions. Front Immunol. 2023;14:1109381.
38. Liu X, Zhang G, Yu T, et al. Exosomes deliver lncRNA DARS-AS1 siRNA to inhibit chronic unpredictable mild stress-induced TNBC metastasis. Cancer Lett. 2022;543:215781.
39. Jiang J, Lu Y, Chu J, et al. Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases. J Nanobiotechnology. 2024;22:159.
40. Wei R, Zhu Y, Zhang Y, et al. AIMP1 promotes multiple myeloma malignancy through interacting with ANP32A to mediate histone H3 acetylation. Cancer Commun. 2022;42:1185-206.
41. Xu S, Liu B, Fan J, et al. Engineered mesenchymal stem cell-derived exosomes with high CXCR4 levels for targeted siRNA gene therapy against cancer. Nanoscale. 2022;14:4098-113.
42. Zhou Y, Yuan Y, Liu M, Hu X, Quan Y, Chen X. Tumor-specific delivery of KRAS siRNA with iRGD-exosomes efficiently inhibits tumor growth. ExRNA. 2019;1:34.
43. Zhang Q, Zhang H, Ning T, et al. Exosome-delivered c-Met siRNA could reverse chemoresistance to cisplatin in gastric cancer. Int J Nanomedicine. 2020;15:2323-35.
44. Yang T, Fogarty B, LaForge B, et al. Delivery of small interfering RNA to inhibit vascular endothelial growth factor in zebrafish using natural brain endothelia cell-secreted exosome nanovesicles for the treatment of brain cancer. AAPS J. 2017;19:475-86.
45. Shokrollahi E, Nourazarian A, Rahbarghazi R, et al. Treatment of human neuroblastoma cell line SH-SY5Y with HSP27 siRNA tagged-exosomes decreased differentiation rate into mature neurons. J Cell Physiol. 2019;234:21005-13.
46. Tang M, Chen Y, Li B, et al. Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis. FASEB J. 2021;35:e21557.
47. Yang J, Luo S, Zhang J, et al. Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson’s disease. Neurobiol Dis. 2021;148:105218.
48. Esteves M, Abreu R, Fernandes H, et al. MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson’s disease. Mol Ther. 2022;30:3176-92.
49. Ghotaslou A, Azizsoltani A, Baghaei K, Alizadeh E. Harnessing HEK293 cell-derived exosomes for hsa-miR-365a-3p delivery: potential application in hepatocellular carcinoma therapy. Heliyon. 2024;10:e29333.
50. Mahati S, Fu X, Ma X, Zhang H, Xiao L. Delivery of miR-26a using an exosomes-based nanosystem inhibited proliferation of hepatocellular carcinoma. Front Mol Biosci. 2021;8:738219.
51. Zhang Z, Luo X, Xue X, et al. Engineered exosomes carrying miR-588 for treatment of triple negative breast cancer through remodeling the immunosuppressive microenvironment. Int J Nanomedicine. 2024;19:743-58.
52. Wan Z, Zhao L, Lu F, et al. Mononuclear phagocyte system blockade improves therapeutic exosome delivery to the myocardium. Theranostics. 2020;10:218-30.
53. Zhang B, Yang Y, Tao R, Yao C, Zhou Z, Zhang Y. Exosomes loaded with miR-665 inhibit the progression of osteosarcoma in vivo and in vitro. Am J Transl Res. 2022;14:7012-26.
54. Nie H, Xie X, Zhang D, et al. Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer. Nanoscale. 2020;12:877-87.
55. Liang G, Kan S, Zhu Y, Feng S, Feng W, Gao S. Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells. Int J Nanomedicine. 2018;13:585-99.
56. Deng W, Meng Y, Wang B, et al.
57. Kim H, Rhee WJ. Exosome-mediated Let7c-5p delivery for breast cancer therapeutic development. Biotechnol Bioprocess Eng. 2020;25:513-20.
58. Zhang K, Dong C, Chen M, et al. Extracellular vesicle-mediated delivery of miR-101 inhibits lung metastasis in osteosarcoma. Theranostics. 2020;10:411-25.
59. Huang T, Jia Z, Fang L, et al. Extracellular vesicle-derived miR-511-3p from hypoxia preconditioned adipose mesenchymal stem cells ameliorates spinal cord injury through the TRAF6/S1P axis. Brain Res Bull. 2022;180:73-85.
60. Zhang A, Bai Z, Yi W, Hu Z, Hao J. Overexpression of miR-338-5p in exosomes derived from mesenchymal stromal cells provides neuroprotective effects by the Cnr1/Rap1/Akt pathway after spinal cord injury in rats. Neurosci Lett. 2021;761:136124.
61. Jahangard Y, Monfared H, Moradi A, Zare M, Mirnajafi-Zadeh J, Mowla SJ. Therapeutic effects of transplanted exosomes containing miR-29b to a rat model of Alzheimer’s disease. Front Neurosci. 2020;14:564.
62. Chivero ET, Liao K, Niu F, et al. Engineered extracellular vesicles loaded with miR-124 attenuate cocaine-mediated activation of microglia. Front Cell Dev Biol. 2020;8:573.
63. Ding Y, Cao F, Sun H, et al. Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression. Cancer Lett. 2019;442:351-61.
64. Yu Y, Jin B, Jia R, et al. Exosomes loaded with the anti-cancer molecule mir-1-3p inhibit intrapulmonary colonization and growth of human esophageal squamous carcinoma cells. J Transl Med. 2024;22:1166.
65. Yang M, Zhou W, Han X, et al. Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer. J Cell Mol Med. 2024;28:e70115.
66. Gu J, You J, Liang H, Zhan J, Gu X, Zhu Y. Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury. J Transl Med. 2024;22:168.
67. Lv Q, Deng J, Chen Y, Wang Y, Liu B, Liu J. Engineered human adipose stem-cell-derived exosomes loaded with miR-21-5p to promote diabetic cutaneous wound healing. Mol Pharm. 2020;17:1723-33.
68. Abbas A, Huang X, Ullah A, et al. Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA. Mol Med. 2024;30:168.
69. Jin Y, Sun L, Chen Y, Lu Y. The homologous tumor-derived-exosomes loaded with miR-1270 selectively enhanced the suppression effect for colorectal cancer cells. Cancer Med. 2024;13:e6936.
70. Mi L, Gao J, Li N, et al. Human umbilical cord mesenchymal stem cell-derived exosomes loaded miR-451a targets ATF2 to improve rheumatoid arthritis. Int Immunopharmacol. 2024;127:111365.
71. Wen J, Chen Y, Liao C, et al. Engineered mesenchymal stem cell exosomes loaded with miR-34c-5p selectively promote eradication of acute myeloid leukemia stem cells. Cancer Lett. 2023;575:216407.
72. Hu J, Liu WF, Zhang XY, et al. Synthetic miR-26a mimics delivered by tumor exosomes repress hepatocellular carcinoma through downregulating lymphoid enhancer factor 1. Hepatol Int. 2023;17:1265-78.
73. Sun X, Song W, Teng L, et al. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogels for corneal epithelial healing. Bioact Mater. 2023;25:640-56.
74. Gao W, Yang N, Yin C, Zeng Y, Zhu X. Engineered exosomes loaded with miR-563 inhibit lung cancer growth. J Oncol. 2022;2022:6141857.
75. Zhao Z, Shuang T, Gao Y, et al. Targeted delivery of exosomal miR-484 reprograms tumor vasculature for chemotherapy sensitization. Cancer Lett. 2022;530:45-58.
76. Sun J, Liu Q, Jiang Y, Cai Z, Liu H, Zuo H. Engineered small extracellular vesicles loaded with miR-654-5p promote ferroptosis by targeting HSPB1 to alleviate sorafenib resistance in hepatocellular carcinoma. Cell Death Discov. 2023;9:362.
77. Duarte-Sanmiguel S, Salazar-Puerta AI, Panic A, et al. ICAM-1-decorated extracellular vesicles loaded with miR-146a and Glut1 drive immunomodulation and hinder tumor progression in a murine model of breast cancer. Biomater Sci. 2023;11:6834-47.
78. Santos NL, Bustos SO, Reis PP, Chammas R, Andrade LNS. Extracellular vesicle-packaged miR-195-5p sensitizes melanoma to targeted therapy with kinase inhibitors. Cells. 2023;12:1317.
79. Luo H, Chen D, Li R, et al. Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis. J Nanobiotechnology. 2023;21:116.
80. Ge L, Wang K, Lin H, et al. Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction. Front Bioeng Biotechnol. 2023;11:1129538.
81. Ohno S, Takanashi M, Sudo K, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21:185-91.
82. Baldari S, Di Rocco G, Magenta A, Picozza M, Toietta G. Extracellular vesicles-encapsulated microRNA-125b produced in genetically modified mesenchymal stromal cells inhibits hepatocellular carcinoma cell proliferation. Cells. 2019;8:1560.
83. Tao SC, Guo SC, Li M, Ke QF, Guo YP, Zhang CQ. Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl Med. 2017;6:736-47.
84. Lou G, Song X, Yang F, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.
85. Katakowski M, Buller B, Zheng X, et al. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013;335:201-4.
86. Ma X, Wang J, Li J, et al. Loading miR-210 in endothelial progenitor cells derived exosomes boosts their beneficial effects on hypoxia/reoxygeneation-injured human endothelial cells via protecting mitochondrial function. Cell Physiol Biochem. 2018;46:664-75.
87. Chen Q, Liu Y, Ding X, et al. Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7. Mol Cell Biochem. 2020;465:103-14.
88. Naseri Z, Oskuee RK, Jaafari MR, Forouzandeh Moghadam M. Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo. Int J Nanomedicine. 2018;13:7727-47.
89. Han S, Li G, Jia M, et al. Delivery of anti-miRNA-221 for colorectal carcinoma therapy using modified cord blood mesenchymal stem cells-derived exosomes. Front Mol Biosci. 2021;8:743013.
90. Kim G, Kim M, Lee Y, Byun JW, Hwang DW, Lee M. Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. J Control Release. 2020;317:273-81.
91. Wang J, Jiang Q, Faleti OD, et al. Exosomal delivery of antagomirs targeting viral and cellular micrornas synergistically inhibits cancer angiogenesis. Mol Ther Nucleic Acids. 2020;22:153-65.
92. Dai H, Luo J, Deng L, et al. Hierarchically injectable hydrogel sequentially delivers antagomiR-467a-3p-loaded and antagomiR-874-5p-loaded satellite-cell-targeting bioengineered extracellular vesicles attenuating sarcopenia. Adv Healthc Mater. 2023;12:e2203056.
93. Monfared H, Jahangard Y, Nikkhah M, Mirnajafi-Zadeh J, Mowla SJ. Potential therapeutic effects of exosomes packed with a miR-21-sponge construct in a rat model of glioblastoma. Front Oncol. 2019;9:782.
94. Wang J, Chen D, Ho EA. Challenges in the development and establishment of exosome-based drug delivery systems. J Control Release. 2021;329:894-906.
95. Fu S, Wang Y, Xia X, Zheng JC. Exosome engineering: current progress in cargo loading and targeted delivery. NanoImpact. 2020;20:100261.
96. Han Y, Jones TW, Dutta S, et al. Overview and update on methods for cargo loading into extracellular vesicles. Processes. 2021;9:356.
97. Zhang D, Lee H, Zhu Z, Minhas JK, Jin Y. Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2017;312:L110-21.
98. Gao J, Li A, Hu J, Feng L, Liu L, Shen Z. Recent developments in isolating methods for exosomes. Front Bioeng Biotechnol. 2022;10:1100892.
99. Lötvall J, Hill AF, Hochberg F, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.
100. Gudbergsson JM, Johnsen KB, Skov MN, Duroux M. Systematic review of factors influencing extracellular vesicle yield from cell cultures. Cytotechnology. 2016;68:579-92.
101. Zheng B, Wang X, Guo M, Tzeng CM. Current development of mesenchymal stem cell-derived extracellular vesicles. Cell Transplant. 2025;34:9636897241297623.
102. Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35:851-8.
103. Johnson J, Shojaee M, Mitchell Crow J, Khanabdali R. From mesenchymal stromal cells to engineered extracellular vesicles: a new therapeutic paradigm. Front Cell Dev Biol. 2021;9:705676.
104. Jia Q, Zhao H, Wang Y, Cen Y, Zhang Z. Mechanisms and applications of adipose-derived stem cell-extracellular vesicles in the inflammation of wound healing. Front Immunol. 2023;14:1214757.
105. Abdulmalek OAAY, Husain KH, AlKhalifa HKAA, Alturani MMAB, Butler AE, Moin ASM. Therapeutic applications of stem cell-derived exosomes. Int J Mol Sci. 2024;25:3562.
106. Yang S, Zhang L, Zhou X, et al. A new large-scale extracellular vesicle production strategy for biomedical drug development. bioRxiv. 2024;bioRxiv:2024-04.15.589541. Available from [accessed 15 July 2025].
107. Liguori GL, Kralj-Iglič V. Pathological and therapeutic significance of tumor-derived extracellular vesicles in cancer cell migration and metastasis. Cancers. 2023;15:4425.
108. Richter M, Piwocka O, Musielak M, Piotrowski I, Suchorska WM, Trzeciak T. From donor to the lab: a fascinating journey of primary cell lines. Front Cell Dev Biol. 2021;9:711381.
109. Escudé Martinez de Castilla P, Tong L, Huang C, et al. Extracellular vesicles as a drug delivery system: a systematic review of preclinical studies. Adv Drug Deliv Rev. 2021;175:113801.
110. Mizenko RR, Feaver M, Bozkurt BT, et al. A critical systematic review of extracellular vesicle clinical trials. J Extracell Vesicles. 2024;13:e12510.
111. Sanz-Ros J, Mas-Bargues C, Romero-García N, Huete-Acevedo J, Dromant M, Borrás C. Extracellular vesicles as therapeutic resources in the clinical environment. Int J Mol Sci. 2023;24:2344.
112. Duong A, Parmar G, Kirkham AM, Burger D, Allan DS. Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review. Cytotherapy. 2023;25:939-45.
113. Elsharkasy OM, Nordin JZ, Hagey DW, et al. Extracellular vesicles as drug delivery systems: why and how? Adv Drug Deliv Rev. 2020;159:332-43.
114. Richter M, Vader P, Fuhrmann G. Approaches to surface engineering of extracellular vesicles. Adv Drug Deliv Rev. 2021;173:416-26.
115. Piccarducci R, Germelli L, Falleni A, et al. GFp farnesylation as a suitable strategy for selectively tagging exosomes. ACS Appl Bio Mater. 2024;7:8305-18.
116. Danilushkina AA, Emene CC, Barlev NA, Gomzikova MO. Strategies for engineering of extracellular vesicles. Int J Mol Sci. 2023;24:13247.
117. Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet. 2022;38:613-26.
118. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007;4:721-6.
119. Dhuri K, Bechtold C, Quijano E, et al. Antisense oligonucleotides: an emerging area in drug discovery and development. J Clin Med. 2020;9:2004.
120. Nguyen VVT, Witwer KW, Verhaar MC, Strunk D, van Balkom BWM. Functional assays to assess the therapeutic potential of extracellular vesicles. J Extracell Vesicles. 2020;10:e12033.
121. Hartjes TA, Mytnyk S, Jenster GW, van Steijn V, van Royen ME. Extracellular vesicle quantification and characterization: common methods and emerging approaches. Bioengineering. 2019;6:7.
122. Vogel R, Savage J, Muzard J, et al. Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge? J Extracell Vesicles. 2021;10:e12052.
123. Mladenović D, Brealey J, Peacock B, Koort K, Zarovni N. Quantitative fluorescent nanoparticle tracking analysis and nano-flow cytometry enable advanced characterization of single extracellular vesicles. J Extracell Biol. 2025;4:e70031.
124. Lennaárd AJ, Mamand DR, Wiklander RJ, El Andaloussi S, Wiklander OPB. Optimised electroporation for loading of extracellular vesicles with doxorubicin. Pharmaceutics. 2021;14:38.
125. Pomatto MAC, Bussolati B, D’Antico S, et al. Improved loading of plasma-derived extracellular vesicles to encapsulate antitumor miRNAs. Mol Ther Methods Clin Dev. 2019;13:133-44.
126. Kooijmans SAA, Stremersch S, Braeckmans K, et al. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release. 2013;172:229-38.
127. Taylor SC, Laperriere G, Germain H. Droplet digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci Rep. 2017;7:2409.
128. Wojnilowicz M, Glab A, Bertucci A, Caruso F, Cavalieri F. Super-resolution imaging of proton sponge-triggered rupture of endosomes and cytosolic release of small interfering RNA. ACS Nano. 2019;13:187-202.
129. Ghanam J, Chetty VK, Zhu X, et al. Single molecule localization microscopy for studying small extracellular vesicles. Small. 2023;19:e2205030.
130. Linares R, Tan S, Gounou C, Brisson AR. Imaging and quantification of extracellular vesicles by transmission electron microscopy. In: Hill AF, Editor. Exosomes and microvesicles. New York: Springer; 2017. pp. 43-54.
131. Bader J, Rüedi P, Mantella V, et al. Loading of extracellular vesicles with nucleic acids via hybridization with non-lamellar liquid crystalline lipid nanoparticles. Adv Sci. 2025;12:e2404860.
132. Ma H, Jia X, Zhang K, Su Z. Cryo-EM advances in RNA structure determination. Signal Transduct Target Ther. 2022;7:58.
133. Pastuzyn ED, Day CE, Kearns RB, et al. The neuronal gene arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer. Cell. 2018;172:275-288.e18.
134. Wang F, Flanagan J, Su N, et al. RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2012;14:22-9.
136. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells. 2019;8:307.
137. Payandeh Z, Tangruksa B, Synnergren J, et al. Extracellular vesicles transport RNA between cells: unraveling their dual role in diagnostics and therapeutics. Mol Aspects Med. 2024;99:101302.
138. O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21:585-606.
139. Buratta S, Tancini B, Sagini K, et al. Lysosomal exocytosis, exosome release and secretory autophagy: the autophagic- and endo-lysosomal systems go extracellular. Int J Mol Sci. 2020;21:2576.
140. Hung ME, Leonard JN. A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery. J Extracell Vesicles. 2016;5:31027.
141. Nakase I, Kogure K, Harashima H, Futaki S. Application of a fusiogenic peptide GALA for intracellular delivery. In: Langel Ü, Editor. Cell-penetrating peptides. Totowa: Humana Press; 2011. pp. 525-33.
142. Qiu C, Xia F, Zhang J, et al. Advanced strategies for overcoming endosomal/lysosomal barrier in nanodrug delivery. Research. 2023;6:0148.
143. Liang X, Gupta D, Xie J, et al. Multimodal engineering of extracellular vesicles for efficient intracellular protein delivery. bioRxiv. 2023;bioRxiv:2023-04.30.535834. Available from [accessed 15 July 2025].
144. Driedonks T, Jiang L, Carlson B, et al. Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina. J Extracell Biol. 2022;1:e59.
145. Wiklander OP, Nordin JZ, O’Loughlin A, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4:26316.
146. Gupta D, Liang X, Pavlova S, et al. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging. J Extracell Vesicles. 2020;9:1800222.
