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Cited by 682Genetic Neurodegenerative DiseasesRNA Interference and Gene DeliveryGenetics and Neurodevelopmental Disorders

RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model

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Harper, Scott Q., Staber, Patrick D., He, Xiaohua, Eliason, Steven L., Martins, Inês H., Mao, Qinwen, Yang, Linda, Kotin, Robert M. +2 more·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0501507102PMC PMC556303
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Abstract

Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD , conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.

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Crossref · 10.1073/pnas.0501507102

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  • Reducing expression of mutant HTT gene using siRNA has emerged as a promising treatment.

    “Recently, reducing the expression of mutant HTT gene using siRNA has emerged as a promising treatment69.”

    From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [69]

    The Abstract and Discussion (page numbers unavailable) support RNA interference as a promising way to reduce mutant htt expression: the authors report improved abnormalities in an HD mouse model. The tested treatment used AAV-delivered short hairpin RNA (shRNA), however, rather than siRNA as the citing sentence specifies. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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  1. [1]The Huntington's Disease Collaborative Research Group (1993) Cell 72, 971–983. [DOI] [PubMed] [Google Scholar]
  2. [2]Gusella, J. F. & MacDonald, M. E. (2000) Nat. Rev. Neurosci. 1, 109–115. [DOI] [PubMed] [Google Scholar]
  3. [3]Ferrante, R. J., Kubilus, J. K., Lee, J., Ryu, H., Beesen, A., Zucker, B., Smith, K., Kowall, N. W., Ratan, R. R., Luthi-Carter, R. & Hersch, S. M. (2003) J. Neurosci. 23, 9418–9427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. [4]Ona, V. O., Li, M., Vonsattel, J. P., Andrews, L. J., Khan, S. Q., Chung, W. M., Frey, A. S., Menon, A. S., Li, X. J., Stieg, P. E., et al. (1999) Nature 399, 263–267. [DOI] [PubMed] [Google Scholar]
  5. [5]Ferrante, R. J., Andreassen, O. A., Dedeoglu, A., Ferrante, K. L., Jenkins, B. G., Hersch, S. M. & Beal, M. F. (2002) J. Neurosci. 22, 1592–1599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [6]Andreassen, O. A., Dedeoglu, A., Ferrante, R. J., Jenkins, B. G., Ferrante, K. L., Thomas, M., Friedlich, A., Browne, S. E., Schilling, G., Borchelt, D. R., et al. (2001) Neurobiol. Dis. 8, 479–491. [DOI] [PubMed] [Google Scholar]
  7. [7]Tanaka, M., Machida, Y., Niu, S., Ikeda, T., Jana, N. R., Doi, H., Kurosawa, M., Nekooki, M. & Nukina, N. (2004) Nat. Med. 10, 148–154. [DOI] [PubMed] [Google Scholar]
  8. [8]Karpuj, M. V., Becher, M. W., Springer, J. E., Chabas, D., Youssef, S., Pedotti, R., Mitchell, D. & Steinman, L. (2002) Nat. Med. 8, 143–149. [DOI] [PubMed] [Google Scholar]
  9. [9]Sanchez, I., Mahlke, C. & Yuan, J. (2003) Nature 421, 373–379. [DOI] [PubMed] [Google Scholar]
  10. [10]Yamamoto, A., Lucas, J. J. & Hen, R. (2000) Cell 101, 57–66. [DOI] [PubMed] [Google Scholar]
  11. [11]Beal, M. F. & Ferrante, R. J. (2004) Nat. Rev. Neurosci. 5, 373–384. [DOI] [PubMed] [Google Scholar]
  12. [12]Levine, M. S., Cepeda, C., Hickey, M. A., Fleming, S. M. & Chesselet, M. F. (2004) Trends Neurosci. 27, 691–697. [DOI] [PubMed] [Google Scholar]
  13. [13]Lin, C. H., Tallaksen-Greene, S., Chien, W. M., Cearley, J. A., Jackson, W. S., Crouse, A. B., Ren, S., Li, X. J., Albin, R. L. & Detloff, P. J. (2001) Hum. Mol. Genet. 10, 137–144. [DOI] [PubMed] [Google Scholar]
  14. [14]Menalled, L. B., Sison, J. D., Dragatsis, I., Zeitlin, S. & Chesselet, M. F. (2003) J. Comp. Neurol. 465, 11–26. [DOI] [PubMed] [Google Scholar]
  15. [15]McBride, J. L., Behrstock, S. P., Chen, E. Y., Jakel, R. J., Siegel, I., Svendsen, C. N. & Kordower, J. H. (2004) J. Comp. Neurol. 475, 211–219. [DOI] [PubMed] [Google Scholar]
  16. [16]Hodgson, J. G., Agopyan, N., Gutekunst, C. A., Leavitt, B. R., LePiane, F., Singaraja, R., Smith, D. J., Bissada, N., McCutcheon, K., Nasir, J., et al. (1999) Neuron 23, 181–192. [DOI] [PubMed] [Google Scholar]
  17. [17]Slow, E. J., van Raamsdonk, J., Rogers, D., Coleman, S. H., Graham, R. K., Deng, Y., Oh, R., Bissada, N., Hossain, S. M., Yang, Y. Z., et al. (2003) Hum. Mol. Genet. 12, 1555–1567. [DOI] [PubMed] [Google Scholar]
  18. [18]Reddy, P. H., Williams, M., Charles, V., Garrett, L., Pike-Buchanan, L., Whetsell, W. O., Jr., Miller, G. & Tagle, D. A. (1998) Nat. Genet. 20, 198–202. [DOI] [PubMed] [Google Scholar]
  19. [19]Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W. & Bates, G. P. (1996) Cell 87, 493–506. [DOI] [PubMed] [Google Scholar]
  20. [20]Schilling, G., Becher, M. W., Sharp, A. H., Jinnah, H. A., Duan, K., Kotzuk, J. A., Slunt, H. H., Ratovitski, T., Cooper, J. K., Jenkins, N. A., et al. (1999) Hum. Mol. Genet. 8, 397–407. [DOI] [PubMed] [Google Scholar]
  21. [21]Dykxhoorn, D. M., Novina, C. D. & Sharp, P. A. (2003) Nat. Rev. Mol. Cell Biol. 4, 457–467. [DOI] [PubMed] [Google Scholar]
  22. [22]Xia, H., Mao, Q., Paulson, H. L. & Davidson, B. L. (2002) Nat. Biotechnol. 20, 1006–1010. [DOI] [PubMed] [Google Scholar]
  23. [23]Urabe, M., Ding, C. & Kotin, R. M. (2002) Hum. Gene Ther. 13, 1935–1943. [DOI] [PubMed] [Google Scholar]
  24. [24]Schilling, G., Jinnah, H. A., Gonzales, V., Coonfield, M. L., Kim, Y., Wood, J. D., Price, D. L., Li, X. J., Jenkins, N., Copeland, N., et al. (2001) Neurobiol. Dis. 8, 405–418. [DOI] [PubMed] [Google Scholar]
  25. [25]Carter, R. J., Lione, L. A., Humby, T., Mangiarini, L., Mahal, A., Bates, G. P., Dunnett, S. B. & Morton, A. J. (1999) J. Neurosci. 19, 3248–3257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. [26]Xia, H., Mao, Q., Eliason, S. L., Harper, S. Q., Martins, I. H., Orr, H. T., Paulson, H. L., Yang, L., Kotin, R. M. & Davidson, B. L. (2004) Nat. Med. 10, 816–820. [DOI] [PubMed] [Google Scholar]
  27. [27]Nance, M. A. & Myers, R. H. (2001) Ment. Retard. Dev. Disabil. Res. Rev. 7, 153–157. [DOI] [PubMed] [Google Scholar]
  28. [28]Fennema-Notestine, C., Archibald, S. L., Jacobson, M. W., Corey-Bloom, J., Paulsen, J. S., Peavy, G. M., Gamst, A. C., Hamilton, J. M., Salmon, D. P. & Jernigan, T. L. (2004) Neurology 63, 989–995. [DOI] [PubMed] [Google Scholar]
  29. [29]Seneca, S., Fagnart, D., Keymolen, K., Lissens, W., Hasaerts, D., Debulpaep, S., Desprechins, B., Liebaers, I. & De Meirleir, L. (2004) Eur. J. Pediatr. 163, 717–721. [DOI] [PubMed] [Google Scholar]
  30. [30]Byers, R. K., Gilles, F. H. & Fung, C. (1973) Neurology 23, 561–569. [DOI] [PubMed] [Google Scholar]
  31. [31]Wheeler, V. C., Gutekunst, C. A., Vrbanac, V., Lebel, L. A., Schilling, G., Hersch, S., Friedlander, R. M., Gusella, J. F., Vonsattel, J. P., Borchelt, D. R. & MacDonald, M. E. (2002) Hum. Mol. Genet. 11, 633–640. [DOI] [PubMed] [Google Scholar]
  32. [32]Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S. & Khvorova, A. (2004) Nat. Biotechnol. 22, 326–330. [DOI] [PubMed] [Google Scholar]
  33. [33]Schwarz, D. S., Hutvagner, G., Du, T., Xu, Z., Aronin, N. & Zamore, P. D. (2003) Cell 115, 199–208. [DOI] [PubMed] [Google Scholar]
  34. [34]Khvorova, A., Reynolds, A. & Jayasena, S. D. (2003) Cell 115, 209–216. [DOI] [PubMed] [Google Scholar]
  35. [35]Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., Ueda, R. & Saigo, K. (2004) Nucleic Acids Res. 32, 936–948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. [36]Djousse, L., Knowlton, B., Cupples, L. A., Marder, K., Shoulson, I. & Myers, R. H. (2002) Neurology 59, 1325–1330. [DOI] [PubMed] [Google Scholar]
  37. [37]Li, S. H., Yu, Z. X., Li, C. L., Nguyen, H. P., Zhou, Y. X., Deng, C. & Li, X. J. (2003) J. Neurosci. 23, 6956–6964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. [38]Kremer, H. P. & Roos, R. A. (1992) Arch. Neurol. (Chicago) 49, 349. [DOI] [PubMed] [Google Scholar]
  39. [39]Nasir, J., Floresco, S. B., O'Kusky, J. R., Diewert, V. M., Richman, J. M., Zeisler, J., Borowski, A., Marth, J. D., Phillips, A. G. & Hayden, M. R. (1995) Cell 81, 811–823. [DOI] [PubMed] [Google Scholar]
  40. [40]Duyao, M. P., Auerbach, A. B., Ryan, A., Persichetti, F., Barnes, G. T., McNeil, S. M., Ge, P., Vonsattel, J. P., Gusella, J. F., Joyner, A. L., et al. (1995) Science 269, 407–410. [DOI] [PubMed] [Google Scholar]
  41. [41]White, J. K., Auerbach, W., Duyao, M. P., Vonsattel, J. P., Gusella, J. F., Joyner, A. L. & MacDonald, M. E. (1997) Nat. Genet. 17, 404–410. [DOI] [PubMed] [Google Scholar]
  42. [42]Dragatsis, I., Levine, M. S. & Zeitlin, S. (2000) Nat. Genet. 26, 300–306. [DOI] [PubMed] [Google Scholar]
  43. [43]Ambrose, C. M., Duyao, M. P., Barnes, G., Bates, G. P., Lin, C. S., Srinidhi, J., Baxendale, S., Hummerich, H., Lehrach, H., Altherr, M., et al. (1994) Somatic Cell Mol. Genet. 20, 27–38. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Authors
Harper, S. Q., Staber, P. D., He, X., Eliason, S. L., Martins, I. H., Mao, Q., Yang, L., Kotin, R. M., Paulson, H. L., & Davidson, B. L.
Affiliations
University of Iowa (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-04-05
Volume
102
Issue
16
Pages
5820-5825
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0501507102
PMC
PMC556303
OpenAlex
W2042739691
Cited by
682
References
3
Citations by year
2026: 11 · 2025: 10 · 2024: 21 · 2023: 9 · 2022: 22 · 2021: 16 · 2020: 19 · 2019: 33 · 2018: 30 · 2017: 28 · 2016: 28 · 2015: 26 · 2014: 38 · 2013: 34 · 2012: 46
FWCI
19.95
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University
  • National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Huntington's disease, RNA interference, mutant huntingtin, polyglutamine expansion, motor impairment, neuropathology, mouse model, gene expression reduction
MeSH terms
Huntingtin Protein, Animals, Cell Line, Disease Models, Animal, Gene Expression Regulation, Humans, Huntington Disease, Mice, Inbred Strains, Motor Activity, Nerve Tissue Proteins, Nuclear Proteins, Genetic Therapy, Gene Transfer Techniques, Gene Silencing, RNA Interference, Mice

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