Current progress on microRNAs-based therapeutics in neurodegenerative diseases

Wiley Interdisciplinary Reviews: RNA

Volumn 8, Issue 3, 2017, Pages

  Pereira, Patrícia ^a   Queiroz, João A ^a   Figueiras, Ana ^a,b   Sousa, Fani ^a  

^a UNIVERSITY OF BEIRA INTERIOR   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

ANTAGOMIR; CYCLODEXTRIN; LIPOSOME; LOCKED NUCLEIC ACID; MESSENGER RNA; MICRORNA; NANOPARTICLE; RECOMBINANT RNA; STAT3 PROTEIN;

3' UNTRANSLATED REGION; 5' UNTRANSLATED REGION; ADENO ASSOCIATED VIRUS; BIOTECHNOLOGY; BLOOD BRAIN BARRIER; BRAIN; CHEMICAL MODIFICATION; DEGENERATIVE DISEASE; DENDRITIC SPINE; DRUG DELIVERY SYSTEM; DRUG MANUFACTURE; DRUG TRANSPORT; GENE EXPRESSION; GENE SILENCING; GENE TARGETING; HUMAN; MICELLE; NERVE CELL PLASTICITY; PROTEIN PHOSPHORYLATION; QUALITY CONTROL; REVIEW; RNA ISOLATION; RNA PURIFICATION; ANIMAL; GENE THERAPY; GENETICS; NEURODEGENERATIVE DISEASES;

ANIMALS; GENETIC THERAPY; HUMANS; MICRORNAS; NEURODEGENERATIVE DISEASES;

EID: 85006070818     PISSN: 17577004     EISSN: 17577012     Source Type: Journal    
DOI: 10.1002/wrna.1409     Document Type: Review

References (135)

1. Satoh J. MicroRNAs and their therapeutic potential for human diseases: aberrant microRNA expression in Alzheimer's disease brains. J Pharmacol Sci 2010, 114:269–275.
2. Soifer HS, Rossi JJ, Saetrom P. MicroRNAs in disease and potential therapeutic applications. Mol Ther 2007, 15:2070–2079.
3. Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, et al. Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 2008, 14:27–41.
4. Grasso M, Piscopo P, Confaloni A, Denti MA. Circulating miRNAs as biomarkers for neurodegenerative disorders. Molecules 2014, 19:6891–6910.
5. Sheinerman KS, Umansky SR. Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies. Front Cell Neurosci 2013, 7:150.
6. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281–297.
7. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008, 9:102–114.
8. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466:835–840.
9. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 2008, 455:58–63.
10. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004, 23:4051–4060.
11. Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 2006, 125:887–901.
12. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science 2004, 303:95–98.
13. Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet 2007, 23:243–249.
14. Gomes AQ, Nolasco S, Soares H. Non-coding RNAs: multi-tasking molecules in the cell. Int J Mol Sci 2013, 14:16010–16039.
15. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009, 136:215–233.
16. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell 2005, 123:1133–1146.
17. Bask I, Patil KS, Alves G, Larsen JP, Meller SG. MicroRNAs as neuroregulatots, biomarkers and therapeutic agents in neurodegenerative diseases. Cell Mol Life Sci 2016, 73:811–827.
18. Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007, 27:435–448.
19. Fineberg SK, Kosik KS, Davidson BL. MicroRNAs potentiate neural development. Neuron 2009, 64:303–309.
20. Ivey KN, Srivastava D. MicroRNAs as developmental regulators. Cold Spring Harb Perspect Biol 2015, 7:a008144.
21. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME. A brain-specific microRNA regulates dendritic spine development. Nature 2006, 439:283–289.
22. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 2010, 466:1105–1109.
23. Liu N, Landreh M, Cao K, Abe M, Hendriks GJ, Kennerdell JR, Zhu Y, Wang LS, Bonini NM. The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature 2012, 482:519–523.
24. Abe M, Bonini NM. MicroRNAs and neurodegeneration: role and impact. Trends Cell Biol 2013, 23:30–36.
25. Goodall EF, Heath PR, Bandmann O, Kirby J, Shaw PJ. Neuronal dark matter: the emerging role of microRNAs in neurodegeneration. Front Cell Neurosci 2013, 7:178.
26. Kocerha J, Kauppinen S, Wahlestedt C. microRNAs in CNS disorders. Neuromolecular Med 2009, 11:162–172.
27. Nelson PT, Wang WX, Rajeev BW. MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol 2008, 18:130–138.
28. Maciotta S, Meregalli M, Torrente Y. The involvement of microRNAs in neurodegenerative diseases. Front Cell Neurosci 2013, 7:265.
29. Morris LG, Veeriah S, Chan TA. Genetic determinants at the interface of cancer and neurodegenerative disease. Oncogene 2010, 29:3453–3464.
30. Serretti A, Olgiati P, De Ronchi D. Genetics of Alzheimer's disease. A rapidly evolving field. J Alzheimers Dis 2007, 12:73–92.
31. Bumcrot D, Manoharan M, Koteliansky V, Sah DW. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2006, 2:711–719.
32. Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 2014, 13:622–638.
33. Magen I, Hornstein E. Oligonucleotide-based therapy for neurodegenerative diseases. Brain Res 2014, 1584:116–128.
34. McDermott AM, Heneghan HM, Miller N, Kerin MJ. The therapeutic potential of microRNAs: disease modulators and drug targets. Pharm Res 2011, 28:3016–3029.
35. van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med 2014, 6:851–864.
36. Zhang Y, Wang Z, Gemeinhart RA. Progress in microRNA delivery. J Control Release 2013, 172:962–974.
37. Beckert B, Masquida B. Synthesis of RNA by in vitro transcription. Methods Mol Biol 2011, 703:29–41.
38. Milligan JF, Groebe DR, Witherell GW, Uhlenbeck OC. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res 1987, 15:8783–8798.
39. Sherlin LD, Bullock TL, Nissan TA, Perona JJ, Lariviere FJ, Uhlenbeck OC, Scaringe SA. Chemical and enzymatic synthesis of tRNAs for high-throughput crystallization. RNA 2001, 7:1671–1678.
40. Marshall WS, Kaiser RJ. Recent advances in the highspeed solid phase synthesis of RNA. Curr Opin Chem Biol 2004, 8:222–229.
41. Pui YH, Ai-Ming Y. Bioengineering of noncoding RNAs for research agents and therapeutics. WIREs RNA 2016, 7:186–197.
42. Gavrilov K, Saltzman WM. Therapeutic siRNA: principles, challenges, and strategies. Yale J Biol Med 2012, 85:187–200.
43. Ozcan G, Ozpolat B, Coleman RL, Sood AK, Lopez-Berestein G. Preclinical and clinical development of siRNA-based therapeutics. Adv Drug Deliv Rev 2015, 87:108–119.
44. Gallas A, Alexander C, Davies MC, Puri S, Allen S. Chemistry and formulations for siRNA therapeutics. Chem Soc Rev 2013, 42:7983.
45. Deng Y, Wang CC, Choy KW, Du Q, Chen J, Wang Q, Li L, Chung TK, Tang T. Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies. Gene 2014, 538:217–227.
46. Chen Q, Wang W, Zeng S, Urayama S, Yu A. A general approach to high-yield biosynthesis of chimeric RNAs bearing various types of functional small RNAs for broad applications. Nucleic Acids Res 2015, 43:3857–3869.
47. Nelissen FH, Leunissen EH, Van de Laar L, Tessari M, Heus HA, Wijmenga SS. Fast production of homogeneous recombinant RNA—towards large-scale production of RNA. Nucleic Acids Res 2012, 40:e102.
48. Martins R, Queiroz JA, Sousa F. Ribonucleic acid purification. J Chromatogr A 2014, 1355:1–14.
49. Dunin-Horkawicz S, Czerwoniec A, Gajda MJ, Feder M, Grosjean H, Bujnicki JM. MODOMICS: a database of RNA modification pathways. Nucleic Acids Res 2006, 34:145–149.
50. Chen S, Ni M, Yu B, Lv T, Lu M, Gong F. Construction and identification of a human liver specific microRNA eukaryotic expression vector. Cell Mol Immunol 2007, 4:473–477.
51. Huang Y, Zou Q, Wang SP, Tang SM, Zhang GZ, Shen XJ. Construction and detection of expression vectors of microRNA-9a in BmN cells. J Zhejiang Univ Sci B 2011, 12:527–533.
52. Ponchon L, Dardel F. Recombinant RNA technology: the tRNA scaffold. Nat Methods 2007, 4:571–576.
53. Ponchon L, Beauvais G, Nonin-Lecomte S, Dardel F. A generic protocol for the expression and purification of recombinant RNA in Escherichia coli using a tRNA scaffold. Nat Protoc 2009, 4:947–959.
54. Liu Y, Stepanov VG, Strych U, Willson RC, Jackson GW, Fox GE. DNAzyme mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli. BMC Biotechnol 2010, 10:85.
55. Ponchon L, Dardel F. Large scale expression and purification of recombinant RNA in Escherichia coli. Methods 2011, 54:267–273.
56. Pereira P, Pedro AQ, Tomás J, Maia CJ, Queiroz JA, Figueiras A, Sousa F. Advances in time course extracellular production of human pre-miR-29b from Rhodovulum sulfidophilum. Appl Microbiol Biotechnol 2016, 100:3723–3734.
57. Suzuki H, Ando T, Umekage S, Tanaka T, Kikuchi Y. Extracellular production of an RNA aptamer by ribonuclease-free marine bacteria harboring engineered plasmids: a proposal for industrial RNA drug production. Appl Environ Microbiol 2010, 76:786–793.
58. Ando T, Suzuki H, Komura K, Tanaka T, Hiraishi A, Kikuchi Y. Extracellular RNAs produced by a marine photosynthetic bacterium Rhodovulum sulfidophilum. Nucleic Acids Symp Ser (Oxf) 2004, 48:165–166.
59. Ando T, Suzuki H, Nishimura S, Tanaka T, Hiraishi A, Kikuchi Y. Characterization of extracellular RNAs produced by the marine photosynthetic bacterium Rhodovulum sulfidophilum. J Biochem 2006, 139:805–811.
60. Duan Z, Yu AM. Bioengineered non-coding RNA agent (BERA) in action. Bioengineered 2016, 14:1–7.
61. Ponchon L, Catala M, Seijo B, El Khouri M, Dardel F, Nonin-Lecomte S, Tisné C. Co-expression of RNA-protein complexes in Escherichia coli and applications to RNA biology. Nucleic Acids Res 2013, 41:e150.
62. Bernardo BC, Charchar FJ, Lin RC, McMullen JR. A microRNA guide for clinicians and basic scientists: background and experimental techniques. Heart Lung Circ 2012, 21:131–142.
63. Tan SC, Yiap BC. DNA, RNA, and protein extraction: the past and the present. J Biomed Biotechnol 2009, 2009:574398.
64. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc 2006, 1:581–585.
65. Vomelova I, Vanickova Z, Sedo A. Methods of RNA purification. All ways (should) lead to Rome. Folia Biol 2009, 55:243–251.
66. Mraz M, Malinova K, Mayer J, Pospisilova S. MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun 2009, 390:1–4.
67. Wei Z, Huang W, Li J, Hou G, Fang J, Yuan Z. Studies on endotoxin removal mechanism of adsorbents with amino acid ligands. J Chromatogr B 2007, 852:288–292.
68. Wassarman KM, Zhang A, Storz G. Small RNAs in Escherichia coli. Trends Microbiol 1999, 7:37–45.
69. Carta G, Jungbauer A. Chromatography media. In: Protein Chromatography: Process Development and Scale-Up. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2010, 85–124. doi:10.1002/9783527630158.ch3.
70. Nunes C, Sousa A, Nunes JC, Morão A, Sousa F, Queiroz JA. Supercoiled plasmid DNA purification by integrating membrane technology with a monolithic chromatography. J Sep Sci 2014, 37:11.
71. Nunes JC, Morão A, Nunes C, Pessoa de Amorim MT, Escobar IC, Queiroz JA. Plasmid DNA recovery from ferementation broths by a combined process of micro- and ultrafiltration: modeling and application. J Membr Sci 2012, 415–416:24–35.
72. Easton LE, Shibata Y, Lukavsky PJ. Rapid, nondenaturing RNA purification using weak anion-exchange fast performance liquid chromatography. RNA 2010, 16:647–653.
73. Kim I, McKenna SA, Viani Puglisi E, Puglisi JD. Rapid purification of RNAs using fast performance liquid chromatography (FPLC). RNA 2007, 13:289–294.
74. Koubek J, Lin KF, Chen YR, Cheng RP, Huang JJ. Strong anion-exchange fast performance liquid chromatography as a versatile tool for preparation and purification of RNA produced by in vitro transcription. RNA 2013, 19:1449–1459.
75. Noll B, Seiffert S, Hertel F, Debelak H, Hadwiger P, Vornlocher HP, Roehl I. Purification of small interfering RNA using nondenaturing anion-exchange chromatography. Nucleic Acid Ther 2011, 21:383–393.
76. Pereira P, Queiroz JA, Figueiras A, Sousa F. Affinity approaches in RNAi-based therapeutics purification. J Chromatogr B Analyt Technol Biomed Life Sci 2016, 1021:45–56.
77. Srisawat C, Engelke DR. Streptavidin aptamers: affinity tags for the study of RNAs and ribonucleoproteins. RNA 2001, 7:632–641.
78. Srisawat C, Goldstein IJ, Engelke DR. Sephadex-binding RNA ligands: rapid affinity purification of RNA from complex RNA mixtures. Nucleic Acids Res 2001, 29:E4.
79. Srisawat C, Engelke DR. RNA affinity tags for purification of RNAs and ribonucleoprotein complexes. Methods 2002, 26:156–161.
80. Walker SC, Scott FH, Srisawat C, Engelke DR. RNA affinity tags for the rapid purification and investigation of RNAs and RNA-protein complexes. Methods Mol Biol 2008, 488:23–40.
81. Sousa F, Prazeres DM, Queiroz JA. Affinity chromatography approaches to overcome the challenges of purifying plasmid DNA. Trends Biotechnol 2008, 26:518–525.
82. Afonso A, Pereira P, Queiroz JA, Sousa A, Sousa F. Purification of pre-miR-29 by a new O-phospho-l-tyrosine affinity chromatographic strategy optimized using design of experiments. J Chromatogr A 2014, 1343:119–127.
83. Pereira P, Sousa A, Queiroz J, Correia I, Figueiras A, Sousa F. Purification of pre-miR-29 by arginine-affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2014, 951–952:16–23.
84. Pereira P, Sousa A, Queiroz J, Figueiras A, Sousa F. New approach for purification of pre-miR-29 using lysine-affinity chromatography. J Chromatogr A 2014, 1331:129–132.
85. Pereira P, Sousa A, Queiroz JA, Figueiras A, Sousa F. Pharmaceutical-grade pre-miR-29 purification using an agmatine monolithic support. J Chromatogr A 2014, 1368:173–182.
86. Lowe CR, Lowe AR, Gupta G. New developments in affinity chromatography with potential application in the production of biopharmaceuticals. J Biochem Biophys Methods 2001, 49:561–574.
87. Ferreira GN, Monteiro GA, Prazeres DM, Cabral JM. Downstream processing of plasmid DNA for gene therapy and DNA vaccine applications. Trends Biotechnol 2000, 18:380–388.
88. Stadler J, Lemmens R, Nyhammar T. Plasmid DNA purification. J Gene Med 2004, 6 (suppl 1):S54–S66.
89. Batkai S, Thum T. Analytical approaches in microRNA therapeutics. J Chromatogr B Analyt Technol Biomed Life Sci 2014, 964:146–152.
90. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005, 33:e179.
91. McGinnis AC, Chen B, Bartlett MG. Chromatographic methods for the determination of therapeutic oligonucleotides. J Chromatogr B Analyt Technol Biomed Life Sci 2012, 883–884:76–94.
92. Moreno-Moya JM, Vilella F, Simon C. MicroRNA: key gene expression regulators. Fertil Steril 2014, 101:1516–1523.
93. Tian T, Wang J, Zhou X. A review: microRNA detection methods. Org Biomol Chem 2015, 13:2226–2238.
94. Pathak A, Patnaik S, Gupta KC. Recent trends in non-viral vector-mediated gene delivery. Biotechnol J 2009, 4:1559–1572.
95. Wittrup A, Lieberman J. Knocking down disease: a progress report on siRNA therapeutic. Nat Rev Genet 2015, 16:543–552.
96. Zhou Y, Zhang C, Liang W. Development of RNAi technology for targeted therapy—a track of siRNA based agents to RNAi therapeutics. J Control Release 2014, 193:270–281.
97. Singh S, Narang AS, Mahato RI. Subcellular fate and off-target effects of siRNA, shRNA, and miRNA. Pharm Res 2011, 28:2996–3015.
98. Wang Z, Rao DD, Senzer N, Nemunaitis J. RNA interference and cancer therapy. Pharm Res 2011, 28:2983–2995.
99. Ballarin-Gonzalez B, Howard KA. Polycation-based nanoparticle delivery of RNAi therapeutics: adverse effects and solutions. Adv Drug Deliv Rev 2012, 64:1717–1729.
100. Edwards RH. Drug delivery via the blood-brain barrier. Nat Neurosci 2001, 4:221–222.
101. Saunders NR, Habgood MD, Møllgård K, Dziegielewska KM. The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system? F1000Res 2016, 5:303.
102. Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 2016, 235:34–47.
103. Azad TD, Pan J, Connolly ID, Remington A, Wilson CM, Grant GA. Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurg Focus 2015, 38:E9.
104. Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, Ahuja A, Akbar M. Strategy for effective brain drug delivery. Eur J Pharm Sci 2010, 40:385–403.
105. Egleton RD, Davis TP. Bioavailability and transport of peptides and peptide drugs into the brain. Peptides 1997, 18:1431–1439.
106. Zhang TT, Li W, Meng G, Wang P, Liao W. Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci 2016, 4:219–229.
107. Pandey PK, Sharma AK, Gupta U. Blood brain barrier: an overview on strategies in drug delivery, realistic in vitro modeling and in vivo live tracking. Tissue Barriers 2015, 4:e1129476.
108. Kusuhara H, Sugiyama Y. Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1). Drug Discov Today 2001, 6:150–156.
109. Bhowmik A, Khan R, Ghosh MK. Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int 2015, 2015:320941.
110. Pangalos MN, Schechter LE, Hurko O. Drug development for CNS disorders: strategies for balancing risk and reducing attrition. Nat Rev Drug Discov 2007, 6:521–532.
111. Pardridge WM. The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2005, 2:3–14.
112. Upadhyay RK. Drug delivery systems, CNS protection, and the blood brain barrier. Biomed Res Int 2014, 2014:869269.
113. Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ. Cellular and molecular barriers to gene-transfer by a cationic lipid. J Biol Chem 1995, 270:18997–19007.
114. Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem Rev 2009, 109:259–302.
115. Robbins PD, Tahara H, Ghivizzani SC. Viral vectors for gene therapy. Trends Biotechnol 1998, 16:35–40.
116. Walther W, Stein U. Viral vectors for gene transfer: a review of their use in the treatment of human diseases. Drugs 2000, 60:249–271.
117. Choudhury SR, Hudry E, Maguire CA, Sena-Esteves M, Breakefield XO, Grandi P. Viral vectors for therapy of neurologic diseases. Neuropharmacology 2016. doi:10.1016/j.neuropharm.2016.02.013.
118. De Smedt SC, Demeester J, Hennink WE. Cationic polymer based gene delivery systems. Pharm Res 2000, 17:113–126.
119. Park TG, Jeong JH, Kim SW. Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 2006, 58:467–486.
120. Chen J, Xie J. Progress on RNAi-based molecular medicines. Int J Nanomedicine 2012, 7:3971–3980.
121. Karim R, Palazzo C, Evrard B, Piel G. Nanocarriers for the treatment of glioblastoma multiforme: current state-of-the-art. J Control Release 2016, 227:23–37.
122. Fonseca-Santos B, Gremião MP, Chorilli M. Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease. Int J Nanomedicine 2015, 10:4981–5003.
123. Mc Carthy DJ, Malhotra M, O'Mahony AM, Cryan JF, O'Driscoll CM. Nanoparticles and the blood-brain barrier: advancing from in-vitro models towards therapeutic significance. Pharm Res 2015, 32:1161–1185.
124. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014, 15:541–555.
125. Gao K, Huang L. Nonviral methods for siRNA delivery. Mol Pharm 2009, 6:651–658.
126. Hart SL. Multifunctional nanocomplexes for gene transfer and gene therapy. Cell Biol Toxicol 2010, 26:69–81.
127. Patil Y, Panyam J. Polymeric nanoparticles for siRNA delivery and gene silencing. Int J Pharm 2009, 367:195–203.
128. Al-Dosari MS, Gao X. Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 2009, 11:671–681.
129. Gupta B, Levchenko TS, Torchilin VP. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev 2005, 57:637–651.
130. Velasco-Aguirre C, Morales F, Gallardo-Toledo E, Guerrero S, Giralt E, Araya E, Kogan MJ. Peptides and proteins used to enhance gold nanoparticle delivery to the brain: preclinical approaches. Int J Nanomedicine 2015, 10:4919–4936.
131. Zhang D, Wang J, Xu D. Cell-penetrating peptides as noninvasive transmembrane vectors for the development of novel multifunctional drug-delivery systems. J Control Release 2016, 229:130–139.
132. Lajoie JM, Shusta EV. Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol 2015, 55:613–631.
133. Sharma G, Lakkadwala S, Modgil A, Singh J. The role of cell-penetrating peptide and transferrin on enhanced delivery of drug to brain. Int J Mol Sci 2016, 17:806–823.
134. Yi X, Kabanov AV. Brain delivery of proteins via their fatty acid and block copolymer modifications. J Drug Target 2013, 21:940–955.
135. Batrakova EV, Miller DW, Li S, Alakhov VY, Kabanov AV, Elmquist WF. Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies. J Pharmacol Exp Ther 2001, 296:551–557.