Clustered Regularly Interspaced Short Palindromic Repeats- Associated Protein Cas9 (CRISPR/Cas9) Terenkapsulasi Nanopartikel Berbasis Hibridisasi Polimer Lipid (LPNs) sebagai Modalitas Mutakhir Terapi pada Huntington’s Disease
Article Sidebar
Published:
Jun 10, 2020
Keywords:
CRISPR/Cas9, huntingtin, Huntington’s Disease, LPNs, mHTT
Main Article Content
Abstract
Introduction: Huntington’s disease (HD) is a rare neurodegenerative disease resulting in motoric, cognitive, and psychiatric dysfunction caused by CAG repeat elongation in the mutated HTT gene (mHTT). Currently, there has not been any effective and efficient curative treatment and there are only symptomatic treatments. To overcome this situation, Clustered Regularly Interspaced Short Palindromic Repeats-Associated Cas9 Protein (CRISPR/Cas9) emerges as a prospective revolutionaire biomolecular approach toward
Huntington’s disease supported by Lipid Polymer Nanoparticles (LPNs) vector with excellent features as a vector that deliver CRISPR Cas9 to the central nerveous system. Objective: As a solution, the objective of this literature review is to identify the potency of CRISPR/Cas9 encapsulated by LPNs as a novel therapeutic strategy against HD. Method:The authors constructed this literature review by analizing and synthesizing 81 full text journal published no longer than 10 years ago that are relevant with the topic discussed in this literature review.
Discussion: CRISPR/Cas9 is able to intervene the N-Terminal of the mutated HTT gene (mHTT) specifically this intervention results in attenuated expression of the mHTT significantly which hamper the expression of reactive astrocyte and prevent further aggregation of the mHTT, thus ameliorate the condition of HD’s patients. LPNs play as vector that deliver CRISPR/Cas9 in order to be able to get through the blood brain barrier. Having low toxicit yand immunogenecity, this vector could improve effectivity and efficiency of this novel therapeutic strategy.
Conclusion : CRISPR/Cas9 encapsulated by LPNs could be a promising novel therapeutic strategy to treat HD efficiently, effectively, and safely.
Keywords: CRISPR/CAS9, huntingtin, Huntington disease, LPNs, mHTT
Article Details
How to Cite
Ilhamsyah, R., Nugrahani, A., & Kurniawan, F. (2020). Clustered Regularly Interspaced Short Palindromic Repeats- Associated Protein Cas9 (CRISPR/Cas9) Terenkapsulasi Nanopartikel Berbasis Hibridisasi Polimer Lipid (LPNs) sebagai Modalitas Mutakhir Terapi pada Huntington’s Disease. JIMKI: Jurnal Ilmiah Mahasiswa Kedokteran Indonesia, 6(2), 87-99. Retrieved from https://bapin-ismki.e-journal.id/jimki/article/view/164
Section
Article Review
References
1. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington's disease: A systematic review and meta-analysis. Movement Disorders. 2012;27(9):1083-1091.
2. Rawlins M, Wexler N, Wexler A, Tabrizi S, Douglas I, Evans S et al. The Prevalence of Huntington's Disease. Neuroepidemiology. 2016;46(2):144-153.
3. WHO | Genes and human disease [Internet]. Who.int. 2016 [cited 24 March 2018]. Available from: http://www.who.int/genomics/public/ geneticdiseases/en/index2.html
4. Goldin I, Mariathasan M. The Butterfly Defect : How Globalization Create Systemic Risks, and What To Do About It. New Jersey: Princeton University Press; 2014.
5. Peggy C. et al. Huntington disease : A Single - Gene Degenerative
Disorder of the Striatum. Clinical Research. 2016.
6. Quarrell O, O’Donovan KL, Bandmann O, Strong M. The prevalence of juvenile Huntington’s disease: a review of the literature and meta-analysis. PLoS Curr. 2012;4.
7. Quaid, K. A. et al. Living at risk: concealing risk and preserving hope in Huntington disease. J. Genet. Couns.2008; 17, 117–128.
8. Van der Meer, L. B., van Duijn, E., Wolterbeek, R. & Tibben, A. Adverse childhood experiences of persons at risk for Huntington’s disease or BRCA1/2 hereditary breast/ovarian cancer. Clin. Genet. 81. 2012; 18– 23.
9. Gillian P.Bates, Ray Dorsey, et al. Huntington Disease. Primer. 2015.
10. Kolli N, Lu M, Maiti P, Rossignol J, Dunbar G. CRISPR-Cas9 Mediated Gene-Silencing of the Mutant Huntingtin Gene in an In Vitro Model of Huntington’s Disease. International Journal of Molecular Sciences. 2017;18(4):754.
11. Junqueiras. Basic Histology Text and Atlas 13th. 2013;179.
12. Zhang L, Zhang L. Lipid–Polymer Hybrid Nanoparticles: Synthesis, Characterization and Applications. Nano LIFE. 2010;01(01n02):163- 173.
13. Ross, C. A. et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat. Rev. Neurol.2014; 10, 204–216.
14. Aiken, C. T. et al. Phosphorylation of threonine 3: implications for huntingtin aggregation and neurotoxicity. J. Biol. Chem. 2009; 284.
15. Wetzel, R. & Mishra, R. in Huntington’s Disease (eds Bates, G. P., Tabrizi, S. J. & Jones, L).2014; 274–322.
16. Zuccato, C. & Cattaneo, E. in Huntington’s Disease (eds Bates, G. P., Tabrizi, S. J. & Jones, L.).2014; 243–273.
17. Nicolas G, Devys D, Goldenberg A, et al. Juvenile Huntington disease in an 18-month-old boy revealed by global developmental delay a reduced cerebellar volume. Am J Med Genet A. 2011;155A(4):815- 818.
18. Klein, F. A. C. et al. Linear and extended: a common polyglutamine conformation recognized by the three antibodies MW1, 1C2 and 3B5H10. Hum. Mol. Genet.2013; 22, 4215– 4223.
19. Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH. 2014. Cystathionine g-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014; 96–100.
20. Chaturvedi RK, Calingasan NY, Yang L, Hennessey T, Johri A, Beal MF. Impairment of PGC-1a expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington’s disease following chronic energy deprivation. Hum Mol Genet 19.2010; 3190–3205.
21. Maria J.S, Floriana L. et al. Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic Strategies. 2018.
22. `Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjo¨rkblomB, Coffey ET, Bagnato C,HanD, et al. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci. 2009; 864– 871.
23. Liot G, Zala D, Pla P, Mottet G, Piel M, Saudou F. Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites. J Neurosci. 2013; 6298–6309.
24. Campesan S, Green EW, Breda C, Sathyasaikumar KV, Muchowski PJ, Schwarcz R, Kyriacou CP, Giorgini
F. 2011. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington’s disease. Curr Biol. 2011; 961–966.
25. Wang, N. et al. Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington disease. Nat. Med. 2014; 536–541.
26. Wang G. et al. Ablation of Huntingtin in adult neurons is nondeleterious but its deletion in young mice causes acute pancreatitis. Proc Natl Acad Sci USA. 2016;113(12):3359-3364.
27. Liu X. et al. N-terminal huntingtin knock-in mice: implications of removing the N-terminal region of
huntingtin for therapy. Plos Genet. 2016;12(5):e1006083.
28. Yang S, Chang R, Yang H, Zhao T, Hong Y, Kong H et al. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. Journal of Clinical Investigation. 2017;127(7):2719- 2724.
29. Monteys AM, Ebanks SA, Keiser MS, Davidson BL. CRISPR/Cas9 editing of the mutant huntingtin allele in vitro and in vivo. Mol Ther. 2017;25(1):12–23.
30. Carroll JB, et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele- specific silencing of mutant huntingtin. Mol Ther. 2011;19(12):2178–2185.
31. Drouet V, et al. Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells. PLoS One. 2014;9(6):e99341.
32. Wang X, Gong Y, Jin B, Wu C, Yang J, Wang L, et al. Long non-coding RNA urothelial carcinoma associated 1 induces cell replication by inhibiting BRG1 in 5637 cells. Oncology reports. 2014;32(3):1281-90.
33. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature protocols. 2013;8(11):2281-308.
34. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21.
35. Kunin V, Sorek R, Hugenholtz P. Evolutionary conservation of sequence and secondary structures in CRISPR repeats. Genome biology. 2007;8(4):R61.
36. Marraffini LA, Sontheimer EJ. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nature reviews Genetics. 2010;11(3):181.
37. Shah SA, Erdmann S, Mojica FJ, Garrett RA. Protospacer recognition motifs: mixed identities and
functional diversity. RNA biology. 2013;10(5):891-9.
38. Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nature medicine. 2015;21(2):121-31.
39. Karvelis T, Gasiunas G, Siksnys V. Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: a brief overview. Methods. 2017.
40. Skotte N, Southwell A, Østergaard M, Carroll J, Warby S, Doty C et al. Allele-Specific Suppression of Mutant Huntingtin Using Antisense Oligonucleotides: Providing a Therapeutic Option for All Huntington Disease Patients. PLoS ONE. 2014;9(9):e107434.
41. Skotte N, Southwell A, Østergaard M, Carroll J, Warby S, Doty C et al. Allele-Specific Suppression of Mutant Huntingtin Using Antisense Oligonucleotides: Providing a Therapeutic Option for All Huntington Disease Patients. PLoS ONE. 2014;9(9):e107434.
42. Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010 Jan 8;327(5962):167-70.
43. Chan A, Jiang J, Chen Y, Li C, Prucha M, Hu Y et al. Progressive Cognitive Deficit, Motor Impairment and Striatal Pathology in a Transgenic Huntington Disease Monkey Model from Infancy to Adulthood. PLOS ONE. 2015;10(5):e0122335.
44. Rangel-Barajas C, Rebec G. Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation. Journal of Huntington's Disease. 2016;5(4):303-331.
45. Morigaki R, Goto S. Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity. Brain Sciences. 2017;7(12):63.
46. Suelves N, Kirkham-McCarthy L, Lahue R, Ginés S. A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington’s disease mice. Scientific Reports. 2017;7(1).
47. Ran F, Hsu P, Wright J, Agarwala V, Scott D, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature Protocols. 2013;8(11):2281-2308.
48. Lalonde S, Stone O, Lessard S, Lavertu A, Desjardins J, Beaudoin M et al. Frameshift indels introduced by genome editing can lead to in-frame exon skipping. PLOS ONE. 2017;12(6):e0178700.
49. Bauer D, Canver M, Orkin S. Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR/Cas9. Journal of Visualized Experiments. 2014;(83).
50. Su T, Liu F, Gu P, Jin H, Chang Y, Wang Q et al. A CRISPR-Cas9 Assisted Non-Homologous End- Joining Strategy for One-step Engineering of Bacterial Genome. Scientific Reports. 2016;6(1).
51. Geisinger J, Turan S, Hernandez S, Spector L, Calos M. In vivoblunt-end cloning through CRISPR/Cas9- facilitated non-homologous end- joining. Nucleic Acids Research. 2016;44(8):e76-e76.
52. Maruyama T, Dougan S, Truttmann M, Bilate A, Ingram J, Ploegh H. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nature Biotechnology. 2015;33(5):538-542.
53. Kaur K, Tandon H, Gupta A, Kumar
M. CrisprGE: a central hub of CRISPR/Cas-based genome editing.Database.2015;2015
54. Nymark M, Sharma A, Sparstad T, Bones A, Winge P. A CRISPR/Cas9 system adapted for gene editing in marine algae. Scientific Reports. 2016;6(1).
55. Naito Y, Hino K,Bono H, Ui-Tei K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites.Bioinformatics.2014;31.1120- 1123.
56. Jiménez Blanco J, Benito J, Ortiz Mellet C, García Fernández J. Molecular nanoparticle-based gene delivery systems. Journal of Drug Delivery Science and Technology. 2017;42:18-37.
57. Naldini L. Gene therapy returns to centre stage. Nature. 2015;526(7573):351-360.
58. Dizaj S, Jafari S, Khosroushahi A. A sight on the current nanoparticle- based gene delivery vectors. Nanoscale Research Letters. 2014;9(1):252.
59. Morachis JM, Mahmoud EA, Sankaranarayanan J, Almutairi A. Triggered rapid degradation of nanoparticles for gene delivery. J Drug Deliv. 2012;9:1–7.
60. Hadinoto K, Sundaresan A, Cheow
W. Lipid–polymer hybrid nanoparticles as a new generation therapeutic delivery platform: A review. European Journal of Pharmaceutics and Biopharmaceutics. 2013;85(3):427- 443.
61. Albanese A, Tang P, Chan W. The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems. Annual Review of Biomedical Engineering. 2012;14(1):1-16.
62. Nitta SK, Numata K. Biopolymer- based nanoparticles for drug/gene delivery and tissue engineering. Int J Mol Sci. 2013;9(1):1629–1654. doi: 10.3390/ijms14011629.
63. Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry. 2017;.
64. Moreno-Vega A, Gómez-Quintero T, Nuñez-Anita R, Acosta-Torres L, Castaño V. Polymeric and Ceramic Nanoparticles in Biomedical Applications. 2012.
65. The Use of Nanoparticles for Gene Therapy in the Nervous System. Journal of Alzheimer's Disease, vol 31. 2012;31:697-710.
66. 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. Journal of Controlled Release. 2016;235:34-47.
67. Lönn P, Kacsinta A, Cui X, Hamil A, Kaulich M, Gogoi K et al. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics. Scientific Reports. 2016;6(1).
68. Qu X, Li P, Liu D, Liu C, Zhang N. Enhanced gene transfer with multilayered polyplexes assembled with layer-by-layer technique. IET Nanobiotechnol. 2012;9(3):122–128. doi: 10.1049/iet-nbt.2011.0031.
69. Gabizon A, Amitay Y, Tzemach D, Gorin J, Shmeeda H, Zalipsky S. Therapeutic efficacy of a lipid-based prodrug of mitomycin C in pegylated liposomes: Studies with human gastro-entero-pancreatic ectopic tumor models. Journal of Controlled Release. 2012;160(2):245-253.
70. Tros de Ilarduya C, Sun Y, Düzgüneş N. Gene delivery by lipoplexes and polyplexes. European Journal of Pharmaceutical Sciences. 2010;40(3):159-170.
71. Wang Q, Shen M, Zhao T, Xu Y, Lin J, Duan Y et al. Low toxicity and long circulation time of Polyampholyte- coated magnetic nanoparticles for blood pool contrast agents. Scientific Reports. 2015;5(1).
72. Lin W, Ma G, Ji F, Zhang J, Wang L, Sun H et al. Biocompatible long- circulating star carboxybetaine polymers. Journal of Materials Chemistry B. 2015;3(3):440-448.
73. Zylberberg C, Gaskill K, Pasley S, Matosevic S. Engineering liposomal nanoparticles for targeted gene therapy. Gene Therapy. 2017;24(8):441-452.
74. Yang J, Bahreman A, Daudey G, Bussmann J, Olsthoorn R, Kros A. Drug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes. ACS Central Science. 2016;2(9):621-630.
75. Konwar R, Ahmed A. NANOPARTICLE: AN OVERVIEW OF PREPARATION, CHARACTERIZATION AND APPLICATION. International Research Journal of Pharmacy. 2016;4(4):47-57.
76. Sah E, Sah H. Recent Trends in Preparation of Poly(lactide-co- glycolide) Nanoparticles by Mixing Polymeric Organic Solution with Antisolvent. 2015.
77. Aili D, Mager M, Roche D, StevensM. Hybrid Nanoparticle−Liposome Detection of Phospholipase Activity.Nano Letters. 2011;11(4):1401-1405.
78. Li X, Anton N, Arpagaus C, Belleteix F, Vandamme T. Nanoparticles by spray drying using innovative new technology: The Büchi Nano Spray Dryer B-90. Journal of Controlled Release. 2010;147(2):304-310.
79. Wang Y, Huang L. Composite Nanoparticles for Gene Delivery. Nonviral Vectors for Gene Therapy - Lipid- and Polymer-based Gene Transfer. 2014;:111-137.
80. Krishnamurthy S, Vaiyapuri R, Zhang L, Chan J. Lipid-coated polymeric nanoparticles for cancer drug delivery. Biomaterials Science. 2015;3(7):923-936.
81. Zhang L, Wang P, Feng Q, Wang N, Chen Z, Huang Y et al. Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy. NPG Asia Materials. 2017;9(10):e441.
2. Rawlins M, Wexler N, Wexler A, Tabrizi S, Douglas I, Evans S et al. The Prevalence of Huntington's Disease. Neuroepidemiology. 2016;46(2):144-153.
3. WHO | Genes and human disease [Internet]. Who.int. 2016 [cited 24 March 2018]. Available from: http://www.who.int/genomics/public/ geneticdiseases/en/index2.html
4. Goldin I, Mariathasan M. The Butterfly Defect : How Globalization Create Systemic Risks, and What To Do About It. New Jersey: Princeton University Press; 2014.
5. Peggy C. et al. Huntington disease : A Single - Gene Degenerative
Disorder of the Striatum. Clinical Research. 2016.
6. Quarrell O, O’Donovan KL, Bandmann O, Strong M. The prevalence of juvenile Huntington’s disease: a review of the literature and meta-analysis. PLoS Curr. 2012;4.
7. Quaid, K. A. et al. Living at risk: concealing risk and preserving hope in Huntington disease. J. Genet. Couns.2008; 17, 117–128.
8. Van der Meer, L. B., van Duijn, E., Wolterbeek, R. & Tibben, A. Adverse childhood experiences of persons at risk for Huntington’s disease or BRCA1/2 hereditary breast/ovarian cancer. Clin. Genet. 81. 2012; 18– 23.
9. Gillian P.Bates, Ray Dorsey, et al. Huntington Disease. Primer. 2015.
10. Kolli N, Lu M, Maiti P, Rossignol J, Dunbar G. CRISPR-Cas9 Mediated Gene-Silencing of the Mutant Huntingtin Gene in an In Vitro Model of Huntington’s Disease. International Journal of Molecular Sciences. 2017;18(4):754.
11. Junqueiras. Basic Histology Text and Atlas 13th. 2013;179.
12. Zhang L, Zhang L. Lipid–Polymer Hybrid Nanoparticles: Synthesis, Characterization and Applications. Nano LIFE. 2010;01(01n02):163- 173.
13. Ross, C. A. et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat. Rev. Neurol.2014; 10, 204–216.
14. Aiken, C. T. et al. Phosphorylation of threonine 3: implications for huntingtin aggregation and neurotoxicity. J. Biol. Chem. 2009; 284.
15. Wetzel, R. & Mishra, R. in Huntington’s Disease (eds Bates, G. P., Tabrizi, S. J. & Jones, L).2014; 274–322.
16. Zuccato, C. & Cattaneo, E. in Huntington’s Disease (eds Bates, G. P., Tabrizi, S. J. & Jones, L.).2014; 243–273.
17. Nicolas G, Devys D, Goldenberg A, et al. Juvenile Huntington disease in an 18-month-old boy revealed by global developmental delay a reduced cerebellar volume. Am J Med Genet A. 2011;155A(4):815- 818.
18. Klein, F. A. C. et al. Linear and extended: a common polyglutamine conformation recognized by the three antibodies MW1, 1C2 and 3B5H10. Hum. Mol. Genet.2013; 22, 4215– 4223.
19. Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH. 2014. Cystathionine g-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014; 96–100.
20. Chaturvedi RK, Calingasan NY, Yang L, Hennessey T, Johri A, Beal MF. Impairment of PGC-1a expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington’s disease following chronic energy deprivation. Hum Mol Genet 19.2010; 3190–3205.
21. Maria J.S, Floriana L. et al. Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic Strategies. 2018.
22. `Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjo¨rkblomB, Coffey ET, Bagnato C,HanD, et al. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci. 2009; 864– 871.
23. Liot G, Zala D, Pla P, Mottet G, Piel M, Saudou F. Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites. J Neurosci. 2013; 6298–6309.
24. Campesan S, Green EW, Breda C, Sathyasaikumar KV, Muchowski PJ, Schwarcz R, Kyriacou CP, Giorgini
F. 2011. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington’s disease. Curr Biol. 2011; 961–966.
25. Wang, N. et al. Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington disease. Nat. Med. 2014; 536–541.
26. Wang G. et al. Ablation of Huntingtin in adult neurons is nondeleterious but its deletion in young mice causes acute pancreatitis. Proc Natl Acad Sci USA. 2016;113(12):3359-3364.
27. Liu X. et al. N-terminal huntingtin knock-in mice: implications of removing the N-terminal region of
huntingtin for therapy. Plos Genet. 2016;12(5):e1006083.
28. Yang S, Chang R, Yang H, Zhao T, Hong Y, Kong H et al. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. Journal of Clinical Investigation. 2017;127(7):2719- 2724.
29. Monteys AM, Ebanks SA, Keiser MS, Davidson BL. CRISPR/Cas9 editing of the mutant huntingtin allele in vitro and in vivo. Mol Ther. 2017;25(1):12–23.
30. Carroll JB, et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele- specific silencing of mutant huntingtin. Mol Ther. 2011;19(12):2178–2185.
31. Drouet V, et al. Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells. PLoS One. 2014;9(6):e99341.
32. Wang X, Gong Y, Jin B, Wu C, Yang J, Wang L, et al. Long non-coding RNA urothelial carcinoma associated 1 induces cell replication by inhibiting BRG1 in 5637 cells. Oncology reports. 2014;32(3):1281-90.
33. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature protocols. 2013;8(11):2281-308.
34. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21.
35. Kunin V, Sorek R, Hugenholtz P. Evolutionary conservation of sequence and secondary structures in CRISPR repeats. Genome biology. 2007;8(4):R61.
36. Marraffini LA, Sontheimer EJ. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nature reviews Genetics. 2010;11(3):181.
37. Shah SA, Erdmann S, Mojica FJ, Garrett RA. Protospacer recognition motifs: mixed identities and
functional diversity. RNA biology. 2013;10(5):891-9.
38. Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nature medicine. 2015;21(2):121-31.
39. Karvelis T, Gasiunas G, Siksnys V. Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: a brief overview. Methods. 2017.
40. Skotte N, Southwell A, Østergaard M, Carroll J, Warby S, Doty C et al. Allele-Specific Suppression of Mutant Huntingtin Using Antisense Oligonucleotides: Providing a Therapeutic Option for All Huntington Disease Patients. PLoS ONE. 2014;9(9):e107434.
41. Skotte N, Southwell A, Østergaard M, Carroll J, Warby S, Doty C et al. Allele-Specific Suppression of Mutant Huntingtin Using Antisense Oligonucleotides: Providing a Therapeutic Option for All Huntington Disease Patients. PLoS ONE. 2014;9(9):e107434.
42. Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010 Jan 8;327(5962):167-70.
43. Chan A, Jiang J, Chen Y, Li C, Prucha M, Hu Y et al. Progressive Cognitive Deficit, Motor Impairment and Striatal Pathology in a Transgenic Huntington Disease Monkey Model from Infancy to Adulthood. PLOS ONE. 2015;10(5):e0122335.
44. Rangel-Barajas C, Rebec G. Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation. Journal of Huntington's Disease. 2016;5(4):303-331.
45. Morigaki R, Goto S. Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity. Brain Sciences. 2017;7(12):63.
46. Suelves N, Kirkham-McCarthy L, Lahue R, Ginés S. A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington’s disease mice. Scientific Reports. 2017;7(1).
47. Ran F, Hsu P, Wright J, Agarwala V, Scott D, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature Protocols. 2013;8(11):2281-2308.
48. Lalonde S, Stone O, Lessard S, Lavertu A, Desjardins J, Beaudoin M et al. Frameshift indels introduced by genome editing can lead to in-frame exon skipping. PLOS ONE. 2017;12(6):e0178700.
49. Bauer D, Canver M, Orkin S. Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR/Cas9. Journal of Visualized Experiments. 2014;(83).
50. Su T, Liu F, Gu P, Jin H, Chang Y, Wang Q et al. A CRISPR-Cas9 Assisted Non-Homologous End- Joining Strategy for One-step Engineering of Bacterial Genome. Scientific Reports. 2016;6(1).
51. Geisinger J, Turan S, Hernandez S, Spector L, Calos M. In vivoblunt-end cloning through CRISPR/Cas9- facilitated non-homologous end- joining. Nucleic Acids Research. 2016;44(8):e76-e76.
52. Maruyama T, Dougan S, Truttmann M, Bilate A, Ingram J, Ploegh H. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nature Biotechnology. 2015;33(5):538-542.
53. Kaur K, Tandon H, Gupta A, Kumar
M. CrisprGE: a central hub of CRISPR/Cas-based genome editing.Database.2015;2015
54. Nymark M, Sharma A, Sparstad T, Bones A, Winge P. A CRISPR/Cas9 system adapted for gene editing in marine algae. Scientific Reports. 2016;6(1).
55. Naito Y, Hino K,Bono H, Ui-Tei K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites.Bioinformatics.2014;31.1120- 1123.
56. Jiménez Blanco J, Benito J, Ortiz Mellet C, García Fernández J. Molecular nanoparticle-based gene delivery systems. Journal of Drug Delivery Science and Technology. 2017;42:18-37.
57. Naldini L. Gene therapy returns to centre stage. Nature. 2015;526(7573):351-360.
58. Dizaj S, Jafari S, Khosroushahi A. A sight on the current nanoparticle- based gene delivery vectors. Nanoscale Research Letters. 2014;9(1):252.
59. Morachis JM, Mahmoud EA, Sankaranarayanan J, Almutairi A. Triggered rapid degradation of nanoparticles for gene delivery. J Drug Deliv. 2012;9:1–7.
60. Hadinoto K, Sundaresan A, Cheow
W. Lipid–polymer hybrid nanoparticles as a new generation therapeutic delivery platform: A review. European Journal of Pharmaceutics and Biopharmaceutics. 2013;85(3):427- 443.
61. Albanese A, Tang P, Chan W. The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems. Annual Review of Biomedical Engineering. 2012;14(1):1-16.
62. Nitta SK, Numata K. Biopolymer- based nanoparticles for drug/gene delivery and tissue engineering. Int J Mol Sci. 2013;9(1):1629–1654. doi: 10.3390/ijms14011629.
63. Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry. 2017;.
64. Moreno-Vega A, Gómez-Quintero T, Nuñez-Anita R, Acosta-Torres L, Castaño V. Polymeric and Ceramic Nanoparticles in Biomedical Applications. 2012.
65. The Use of Nanoparticles for Gene Therapy in the Nervous System. Journal of Alzheimer's Disease, vol 31. 2012;31:697-710.
66. 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. Journal of Controlled Release. 2016;235:34-47.
67. Lönn P, Kacsinta A, Cui X, Hamil A, Kaulich M, Gogoi K et al. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics. Scientific Reports. 2016;6(1).
68. Qu X, Li P, Liu D, Liu C, Zhang N. Enhanced gene transfer with multilayered polyplexes assembled with layer-by-layer technique. IET Nanobiotechnol. 2012;9(3):122–128. doi: 10.1049/iet-nbt.2011.0031.
69. Gabizon A, Amitay Y, Tzemach D, Gorin J, Shmeeda H, Zalipsky S. Therapeutic efficacy of a lipid-based prodrug of mitomycin C in pegylated liposomes: Studies with human gastro-entero-pancreatic ectopic tumor models. Journal of Controlled Release. 2012;160(2):245-253.
70. Tros de Ilarduya C, Sun Y, Düzgüneş N. Gene delivery by lipoplexes and polyplexes. European Journal of Pharmaceutical Sciences. 2010;40(3):159-170.
71. Wang Q, Shen M, Zhao T, Xu Y, Lin J, Duan Y et al. Low toxicity and long circulation time of Polyampholyte- coated magnetic nanoparticles for blood pool contrast agents. Scientific Reports. 2015;5(1).
72. Lin W, Ma G, Ji F, Zhang J, Wang L, Sun H et al. Biocompatible long- circulating star carboxybetaine polymers. Journal of Materials Chemistry B. 2015;3(3):440-448.
73. Zylberberg C, Gaskill K, Pasley S, Matosevic S. Engineering liposomal nanoparticles for targeted gene therapy. Gene Therapy. 2017;24(8):441-452.
74. Yang J, Bahreman A, Daudey G, Bussmann J, Olsthoorn R, Kros A. Drug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes. ACS Central Science. 2016;2(9):621-630.
75. Konwar R, Ahmed A. NANOPARTICLE: AN OVERVIEW OF PREPARATION, CHARACTERIZATION AND APPLICATION. International Research Journal of Pharmacy. 2016;4(4):47-57.
76. Sah E, Sah H. Recent Trends in Preparation of Poly(lactide-co- glycolide) Nanoparticles by Mixing Polymeric Organic Solution with Antisolvent. 2015.
77. Aili D, Mager M, Roche D, StevensM. Hybrid Nanoparticle−Liposome Detection of Phospholipase Activity.Nano Letters. 2011;11(4):1401-1405.
78. Li X, Anton N, Arpagaus C, Belleteix F, Vandamme T. Nanoparticles by spray drying using innovative new technology: The Büchi Nano Spray Dryer B-90. Journal of Controlled Release. 2010;147(2):304-310.
79. Wang Y, Huang L. Composite Nanoparticles for Gene Delivery. Nonviral Vectors for Gene Therapy - Lipid- and Polymer-based Gene Transfer. 2014;:111-137.
80. Krishnamurthy S, Vaiyapuri R, Zhang L, Chan J. Lipid-coated polymeric nanoparticles for cancer drug delivery. Biomaterials Science. 2015;3(7):923-936.
81. Zhang L, Wang P, Feng Q, Wang N, Chen Z, Huang Y et al. Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy. NPG Asia Materials. 2017;9(10):e441.