Combination of Genetics and Nanotechnology for Down Syndrome Modification: A Potential Hypothesis and Review of the Literature
Abstract
Down syndrome (DS) is one of the most prevalent genetic disorders in humans. The use of new approaches in genetic engineering and nanotechnology methods in combination with natural cellular phenomenon can modify the disease in affected people. We consider two CRISPR/Cas9 systems to cut a specific region from short arm of the chromosome 21 (Chr21) and replace it with a novel designed DNA construct, containing the essential genes in chromatin remodeling for inactivating of an extra Chr21. This requires mimicking of the natural cellular pattern for inactivation of the extra X chromosome in females. By means of controlled dosage of an appropriate Nano-carrier (a surface engineered Poly D, L-lactide-co-glycolide (PLGA) for integrating the relevant construct in Trisomy21 brain cell culture media and then in DS mouse model, we would be able to evaluate the modification and the reduction of the active extra Chr21 and in turn reduce substantial adverse effects of the disease, like intellectual disabilities. The hypothesis and study seek new insights in Down syndrome modification.
1. Blank M, Fuerst PG, Stevens B et al (2011). The Down syndrome critical region regulates retinogeniculate refinement. J Neurosci, 31:5764-5776.
2. Chatterjee A, Dutta S, Sinha S, Mukhopadhyay K (2011). Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome. Dis Markers, 31:247-257.
3. Jones KL, Jones MC, Del Campo M (2013). Smith's Recognizable Patterns of Human Malformation E-Book. ed. Elsevier Health Sciences.
4. Wald NJ, Huttly WJ, Hackshaw AK (2003). Antenatal screening for Down's syndrome with the quadruple test. Lancet, 361:835-836.
5. Palomaki GE, Deciu C, Kloza EM et al (2012). DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med, 14:296-305.
6. Palomaki GE, Kloza EM, Lambert-Messerlian GM et al (2011). DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med, 13:913-920.
7. Ali FE, Al-Busairi WA, Al-Mulla FA (1999). Treatment of hyperthyroidism in Down syndrome: case report and review of the literature. Res Dev Disabil, 20:297-303.
8. Lee J-E, Jang H, Cho E-J, Youn H-D (2009). Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin. Exp Mol Med, 41:471-477.
9. Rissman RA, Mobley WC (2011). Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer’s disease. J Neurochem, 117:613-622.
10. Das D, Phillips C, Hsieh W et al (2014). Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome. Prog Neuropsychopharmacol Biol Psychiatry, 54:140-148.
11. McCabe LL, McCabe ER (2013). Down syndrome and personalized medicine: Changing paradigms from genotype to phenotype to treatment. Congenit Anom (Kyoto), 53:1-2.
12. Shapiro B (1999). The Down syndrome critical region. In: The Molecular Biology of Down Syndrome. Ed(s): Springer, pp. 41-60.
13. Hamosh Ada SPM (2010). Down syndrome critical region gene 4. https://www.omim.org/entry/604829
14. Pelleri MC, Cicchini E, Locatelli C et al (2016). Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22. 13 as critical to the phenotype. Hum Mol Genet, 25:2525-2538.
15. Berletch JB, Yang F, Disteche CM (2010). Escape from X inactivation in mice and humans. Genome Biol, 11:213.
16. Berletch JB, Yang F, Xu J, Carrel L, Disteche CM (2011). Genes that escape from X inactivation. Hum Genet, 130:237-245.
17. Rots M (2014). CRISPR-Cas, Zinc Fingers and Epigenetic Editing with Dr. Marianne Rots. Epigenetics, 2.
18. Cong L, Ran FA, Cox D, Lin S et al (2013). Multiplex genome engineering using CRISPR/Cas systems. Science, 339:819-823.
19. Mali P, Yang L, Esvelt KM et al (2013). RNA-guided human genome engineering via Cas9. Science, 339:823-826.
20. Jinek M, East A, Cheng A et al (2013). RNA-programmed genome editing in human cells. Elife, 2:e00471.
21. Men K, Duan X, He Z et al (2017). CRISPR/Cas9-mediated correction of human genetic disease. Sci China Life Sci. 60:447–457.
22. Qi LS, Larson MH, Gilbert LA et al (2013). Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell, 152:1173-1183.
23. Zalatan JG, Lee ME, Almeida R et al (2015). Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell, 160:339-350.
24. Kiani S, Beal J, Ebrahimkhani MR et al (2014). CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods, 11:723-726.
25. Song B, Fan Y, He W et al (2015). Improved hematopoietic differentiation efficiency of gene-corrected beta-thalassemia induced pluripotent stem cells by CRISPR/Cas9 system. Stem Cells Dev, 24:1053-1065.
26. Savić N, Schwank G (2016). Advances in therapeutic CRISPR/Cas9 genome editing. Transl Res, 168:15-21.
27. Yoshimi K, Kaneko T, Voigt B, Mashimo T (2014). Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR–Cas platform. Nat Commun, 5:4240.
28. Komor AC, Badran AH, Liu DR (2017). CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell, 169(3):559.
29. Sun W, Ji W, Hall JM et al (2015). Self‐Assembled DNA Nanoclews for the Efficient Delivery of CRISPR–Cas9 for Genome Editing. Angew Chem Int Ed Engl, 54:12029-12033.
30. Jiang C, Mei M, Li B et al (2017). A non-viral CRISPR/Cas9 delivery system for therapeutic gene targeting in vivo. Cell Res, 27:440-443.
31. Yang F, Babak T, Shendure J, Disteche CM (2010). Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res, 20:614-622.
32. Gardiner K (1997). Clonability and gene distribution on human chromosome 21: reflections of junk DNA content? Gene, 205:39-46.
33. Song R, Ro S, Michaels JD et al (2009). Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nat Genet, 41:488-493.
34. Al Nadaf S, Deakin JE, Gilbert C et al (2012). A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation. Chromosoma, 121:71-78.
35. Heard E (2005). Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome. Curr Opin Genet Dev, 15:482-489.
36. Reinius B, Shi C, Hengshuo L et al (2010). Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse. BMC Genomics, 11:614.
37. Berletch JB, Ma W, Yang F et al (2015). Escape from X inactivation varies in mouse tissues. PLoS Genet, 11:e1005079.
38. Keown CL, Berletch JB, Castanon R et al (2017). Allele-specific non-CG DNA methylation marks domains of active chromatin in female mouse brain. Proc Natl Acad Sci U S A, 114:E2882-E2890.
39. Yu S, Yi H, Wang Z, Dong J (2015). Screening key genes associated with congenital heart defects in Down syndrome based on differential expression network. Int J Clin Exp Pathol, 8:8385-93.
40. Yu W, Liang R, Yang L et al (2007). Screening and identification of human chromosome 21 genes resultingin abnormal development of fetal cerebral cortex with Down syndrome]. Zhonghua Yi Xue Za Zhi, 87:2759-2763.
41. Sommer CA, Pavarino-Bertelli EC, Goloni-Bertollo EM et al (2008). Identification of dysregulated genes in lymphocytes from children with Down syndrome. Genome, 51:19-29.
42. Gordon J, Amini S, White MK (2013). General overview of neuronal cell culture. Methods Mol Biol, 1078:1-8.
43. Ray B, Chopra N, Long JM, Lahiri DK (2014). Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research. Mol Brain, 7:63.
44. Braudeau J, Dauphinot L, Duchon A et al (2011). Chronic Treatment with a Promnesiant GABA-A α5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a DownSyndrome Mouse Model. Adv Pharmacol Sci, 2011:153218.
45. Miyamoto K, Suzuki N, Sakai K et al (2014). A novel mouse model for Down syndrome that harbor a single copy of human artificial chromosome (HAC) carrying a limited number of genes from human chromosome 21. Transgenic Res, 23:317-329.
46. Reddy LH, Sharma R, Chuttani K et al (2005). Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid lipid nanoparticles in Dalton's lymphoma tumor bearing mice. J Control Release, 105:185-198.
47. Mout R, Ray M, Yesilbag Tonga G et al (2017). Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing. ACS Nano, 11:2452-2458.
48. Slaymaker IM, Gao L, Zetsche B et al (2016). Rationally engineered Cas9 nucleases with improved specificity. Science, 351:84-88.
49. Kleinstiver BP, Pattanayak V, Prew MS et al (2016). High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects. Nature, 529:490-495.
50. Dow LE, Fisher J, O'rourke KP et al (2015). Inducible in vivo genome editing with CRISPR-Cas9. Nat Biotechnol, 33:390-394.
51. Solaro R, Chiellini F, Battisti A (2010). Targeted delivery of protein drugs by nanocarriers. Materials (Basel), 3:1928-1980.
52. Bala I, Hariharan S, Kumar MR (2004). PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst, 21:387-422.
53. Weiss CK, Kohnle MV, Landfester K et al (2008). The First Step into the Brain: Uptake of NIO‐PBCA Nanoparticles by Endothelial Cells in vitro and in vivo, and Direct Evidence for their Blood–Brain Barrier Permeation. Chem Med Chem, 3:1395-1403.
54. Bose RJ, Lee S-H, Park H (2016). Lipid-based surface engineering of PLGA nanoparticles for drug and gene delivery applications. Biomater Res, 20:34.
55. Wang L, Li Z, Song X et al (2016). Bioinformatic analysis of genes and MicroRNAs associated with atrioventricular septal defect in down syndrome patients. Int Heart J, 57:490-495.
2. Chatterjee A, Dutta S, Sinha S, Mukhopadhyay K (2011). Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome. Dis Markers, 31:247-257.
3. Jones KL, Jones MC, Del Campo M (2013). Smith's Recognizable Patterns of Human Malformation E-Book. ed. Elsevier Health Sciences.
4. Wald NJ, Huttly WJ, Hackshaw AK (2003). Antenatal screening for Down's syndrome with the quadruple test. Lancet, 361:835-836.
5. Palomaki GE, Deciu C, Kloza EM et al (2012). DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med, 14:296-305.
6. Palomaki GE, Kloza EM, Lambert-Messerlian GM et al (2011). DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med, 13:913-920.
7. Ali FE, Al-Busairi WA, Al-Mulla FA (1999). Treatment of hyperthyroidism in Down syndrome: case report and review of the literature. Res Dev Disabil, 20:297-303.
8. Lee J-E, Jang H, Cho E-J, Youn H-D (2009). Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin. Exp Mol Med, 41:471-477.
9. Rissman RA, Mobley WC (2011). Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer’s disease. J Neurochem, 117:613-622.
10. Das D, Phillips C, Hsieh W et al (2014). Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome. Prog Neuropsychopharmacol Biol Psychiatry, 54:140-148.
11. McCabe LL, McCabe ER (2013). Down syndrome and personalized medicine: Changing paradigms from genotype to phenotype to treatment. Congenit Anom (Kyoto), 53:1-2.
12. Shapiro B (1999). The Down syndrome critical region. In: The Molecular Biology of Down Syndrome. Ed(s): Springer, pp. 41-60.
13. Hamosh Ada SPM (2010). Down syndrome critical region gene 4. https://www.omim.org/entry/604829
14. Pelleri MC, Cicchini E, Locatelli C et al (2016). Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22. 13 as critical to the phenotype. Hum Mol Genet, 25:2525-2538.
15. Berletch JB, Yang F, Disteche CM (2010). Escape from X inactivation in mice and humans. Genome Biol, 11:213.
16. Berletch JB, Yang F, Xu J, Carrel L, Disteche CM (2011). Genes that escape from X inactivation. Hum Genet, 130:237-245.
17. Rots M (2014). CRISPR-Cas, Zinc Fingers and Epigenetic Editing with Dr. Marianne Rots. Epigenetics, 2.
18. Cong L, Ran FA, Cox D, Lin S et al (2013). Multiplex genome engineering using CRISPR/Cas systems. Science, 339:819-823.
19. Mali P, Yang L, Esvelt KM et al (2013). RNA-guided human genome engineering via Cas9. Science, 339:823-826.
20. Jinek M, East A, Cheng A et al (2013). RNA-programmed genome editing in human cells. Elife, 2:e00471.
21. Men K, Duan X, He Z et al (2017). CRISPR/Cas9-mediated correction of human genetic disease. Sci China Life Sci. 60:447–457.
22. Qi LS, Larson MH, Gilbert LA et al (2013). Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell, 152:1173-1183.
23. Zalatan JG, Lee ME, Almeida R et al (2015). Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell, 160:339-350.
24. Kiani S, Beal J, Ebrahimkhani MR et al (2014). CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods, 11:723-726.
25. Song B, Fan Y, He W et al (2015). Improved hematopoietic differentiation efficiency of gene-corrected beta-thalassemia induced pluripotent stem cells by CRISPR/Cas9 system. Stem Cells Dev, 24:1053-1065.
26. Savić N, Schwank G (2016). Advances in therapeutic CRISPR/Cas9 genome editing. Transl Res, 168:15-21.
27. Yoshimi K, Kaneko T, Voigt B, Mashimo T (2014). Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR–Cas platform. Nat Commun, 5:4240.
28. Komor AC, Badran AH, Liu DR (2017). CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell, 169(3):559.
29. Sun W, Ji W, Hall JM et al (2015). Self‐Assembled DNA Nanoclews for the Efficient Delivery of CRISPR–Cas9 for Genome Editing. Angew Chem Int Ed Engl, 54:12029-12033.
30. Jiang C, Mei M, Li B et al (2017). A non-viral CRISPR/Cas9 delivery system for therapeutic gene targeting in vivo. Cell Res, 27:440-443.
31. Yang F, Babak T, Shendure J, Disteche CM (2010). Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res, 20:614-622.
32. Gardiner K (1997). Clonability and gene distribution on human chromosome 21: reflections of junk DNA content? Gene, 205:39-46.
33. Song R, Ro S, Michaels JD et al (2009). Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nat Genet, 41:488-493.
34. Al Nadaf S, Deakin JE, Gilbert C et al (2012). A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation. Chromosoma, 121:71-78.
35. Heard E (2005). Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome. Curr Opin Genet Dev, 15:482-489.
36. Reinius B, Shi C, Hengshuo L et al (2010). Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse. BMC Genomics, 11:614.
37. Berletch JB, Ma W, Yang F et al (2015). Escape from X inactivation varies in mouse tissues. PLoS Genet, 11:e1005079.
38. Keown CL, Berletch JB, Castanon R et al (2017). Allele-specific non-CG DNA methylation marks domains of active chromatin in female mouse brain. Proc Natl Acad Sci U S A, 114:E2882-E2890.
39. Yu S, Yi H, Wang Z, Dong J (2015). Screening key genes associated with congenital heart defects in Down syndrome based on differential expression network. Int J Clin Exp Pathol, 8:8385-93.
40. Yu W, Liang R, Yang L et al (2007). Screening and identification of human chromosome 21 genes resultingin abnormal development of fetal cerebral cortex with Down syndrome]. Zhonghua Yi Xue Za Zhi, 87:2759-2763.
41. Sommer CA, Pavarino-Bertelli EC, Goloni-Bertollo EM et al (2008). Identification of dysregulated genes in lymphocytes from children with Down syndrome. Genome, 51:19-29.
42. Gordon J, Amini S, White MK (2013). General overview of neuronal cell culture. Methods Mol Biol, 1078:1-8.
43. Ray B, Chopra N, Long JM, Lahiri DK (2014). Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research. Mol Brain, 7:63.
44. Braudeau J, Dauphinot L, Duchon A et al (2011). Chronic Treatment with a Promnesiant GABA-A α5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a DownSyndrome Mouse Model. Adv Pharmacol Sci, 2011:153218.
45. Miyamoto K, Suzuki N, Sakai K et al (2014). A novel mouse model for Down syndrome that harbor a single copy of human artificial chromosome (HAC) carrying a limited number of genes from human chromosome 21. Transgenic Res, 23:317-329.
46. Reddy LH, Sharma R, Chuttani K et al (2005). Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid lipid nanoparticles in Dalton's lymphoma tumor bearing mice. J Control Release, 105:185-198.
47. Mout R, Ray M, Yesilbag Tonga G et al (2017). Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing. ACS Nano, 11:2452-2458.
48. Slaymaker IM, Gao L, Zetsche B et al (2016). Rationally engineered Cas9 nucleases with improved specificity. Science, 351:84-88.
49. Kleinstiver BP, Pattanayak V, Prew MS et al (2016). High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects. Nature, 529:490-495.
50. Dow LE, Fisher J, O'rourke KP et al (2015). Inducible in vivo genome editing with CRISPR-Cas9. Nat Biotechnol, 33:390-394.
51. Solaro R, Chiellini F, Battisti A (2010). Targeted delivery of protein drugs by nanocarriers. Materials (Basel), 3:1928-1980.
52. Bala I, Hariharan S, Kumar MR (2004). PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst, 21:387-422.
53. Weiss CK, Kohnle MV, Landfester K et al (2008). The First Step into the Brain: Uptake of NIO‐PBCA Nanoparticles by Endothelial Cells in vitro and in vivo, and Direct Evidence for their Blood–Brain Barrier Permeation. Chem Med Chem, 3:1395-1403.
54. Bose RJ, Lee S-H, Park H (2016). Lipid-based surface engineering of PLGA nanoparticles for drug and gene delivery applications. Biomater Res, 20:34.
55. Wang L, Li Z, Song X et al (2016). Bioinformatic analysis of genes and MicroRNAs associated with atrioventricular septal defect in down syndrome patients. Int Heart J, 57:490-495.
| Files | ||
| Issue | Vol 48 No 3 (2019) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i3.878 | |
| Keywords | ||
| Down syndrome CRISPR/Cas9 Designed DNA construct Poly D L-lactide-co-glycolide (PLGA) Nano-carrier Chromosome 21 inactivation | ||
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How to Cite
1.
TAFAZOLI A, BEHJATI F, FARHUD DD, ABBASZADEGAN MR. Combination of Genetics and Nanotechnology for Down Syndrome Modification: A Potential Hypothesis and Review of the Literature. Iran J Public Health. 2019;48(3):371-378.
