Safe and Efficient Silencing with a Pol II, but Not a Pol lII, Promoter Expressing an Artificial miRNA Targeting Human Huntingtin

Molecular Therapy Nucleic Acids

Volumn 7, Issue , 2017, Pages 324-334

  Pfister, Edith L ^a   Chase, Kathryn O ^a   Sun, Huaming ^a   Kennington, Lori A ^a   Conroy, Faith ^a   Johnson, Emily ^a,b   Miller, Rachael ^a   Borel, Florie ^a   Aronin, Neil ^a   Mueller, Christian ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

AAV; gene therapy; HTT; huntingtin; Huntington's disease; miRNA; RNAi; shRNA

Indexed keywords

ADENO ASSOCIATED VIRUS VECTOR; COMPLEMENTARY DNA; HUNTINGTIN; MICRORNA; MICRORNA 155; PLASMID DNA;

ADENO ASSOCIATED VIRUS 9; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DEGENERATIVE DISEASE; GENE EXPRESSION; GENE MUTATION; GENE TARGETING; HELA CELL LINE; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; IMMUNOHISTOCHEMISTRY; MOUSE; NEUROLOGIC DISEASE; NONHUMAN; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROMOTER REGION; RNA INTERFERENCE; RNA SEQUENCE; RNA TARGETING; RNAI THERAPEUTICS; TRANSGENIC MOUSE; TREATMENT OUTCOME; WALKING;

EID: 85020724380     PISSN: None     EISSN: 21622531     Source Type: Journal    
DOI: 10.1016/j.omtn.2017.04.011     Document Type: Article

References (36)

1. 1 Huntington, T., Macdonald, M.E., Ambrose, C.M., Duyao, M.P., Myers, R.H., Lin, C., et al., The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72 (1993), 971–983.
2. 2 Sharp, A.H., Loev, S.J., Schilling, G., Li, S.H., Li, X.J., Bao, J., Wagster, M.V., Kotzuk, J.A., Steiner, J.P., Lo, A., et al. Widespread expression of Huntington's disease gene (IT15) protein product. Neuron 14 (1995), 1065–1074.
3. 3 Graveland, G.A., Williams, R.S., DiFiglia, M., Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 227 (1985), 770–773.
4. 4 Kordasiewicz, H.B., Stanek, L.M., Wancewicz, E.V., Mazur, C., McAlonis, M.M., Pytel, K.A., Artates, J.W., Weiss, A., Cheng, S.H., Shihabuddin, L.S., et al. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 74 (2012), 1031–1044.
5. 5 Borel, F., Kay, M.A., Mueller, C., Recombinant AAV as a platform for translating the therapeutic potential of RNA interference. Mol. Ther. 22 (2014), 692–701.
6. 6 Stanek, L.M., Sardi, S.P., Mastis, B., Richards, A.R., Treleaven, C.M., Taksir, T., Misra, K., Cheng, S.H., Shihabuddin, L.S., Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of Huntington's disease. Hum. Gene Ther. 25 (2014), 461–474.
7. 7 Boudreau, R.L., McBride, J.L., Martins, I., Shen, S., Xing, Y., Carter, B.J., Davidson, B.L., Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol. Ther. 17 (2009), 1053–1063.
8. 8 McBride, J.L., Boudreau, R.L., Harper, S.Q., Staber, P.D., Monteys, A.M., Martins, I., Gilmore, B.L., Burstein, H., Peluso, R.W., Polisky, B., et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc. Natl. Acad. Sci. U S A 105 (2008), 5868–5873.
9. 9 Gu, S., Jin, L., Zhang, Y., Huang, Y., Zhang, F., Valdmanis, P.N., Kay, M.A., The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo. Cell 151 (2012), 900–911.
10. 10 Grimm, D., Streetz, K.L., Jopling, C.L., Storm, T.A., Pandey, K., Davis, C.R., Marion, P., Salazar, F., Kay, M.A., Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441 (2006), 537–541.
11. 11 Grimm, D., Wang, L., Lee, J.S., Schürmann, N., Gu, S., Börner, K., Storm, T.A., Kay, M.A., Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver. J. Clin. Invest. 120 (2010), 3106–3119.
12. 12 Bish, L.T., Sleeper, M.M., Reynolds, C., Gazzara, J., Withnall, E., Singletary, G.E., Buchlis, G., Hui, D., High, K.A., Gao, G., et al. Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines. Hum. Gene Ther. 22 (2011), 969–977.
13. 13 Martin, J.N., Wolken, N., Brown, T., Dauer, W.T., Ehrlich, M.E., Gonzalez-Alegre, P., Lethal toxicity caused by expression of shRNA in the mouse striatum: implications for therapeutic design. Gene Ther. 18 (2011), 666–673.
14. 14 van Gestel, M.A., van Erp, S., Sanders, L.E., Brans, M.A.D., Luijendijk, M.C.M., Merkestein, M., Pasterkamp, R.J., Adan, R.A., shRNA-induced saturation of the microRNA pathway in the rat brain. Gene Ther. 21 (2014), 205–211.
15. 15 Valdmanis, P.N., Gu, S., Chu, K., Jin, L., Zhang, F., Munding, E.M., Zhang, Y., Huang, Y., Kutay, H., Ghoshal, K., et al. RNA interference-induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in mice. Nat. Med. 22 (2016), 557–562.
16. 16 Toro Cabrera, G., Mueller, C., Design of shRNA and miRNA for delivery to the CNS. Methods Mol. Biol. 1382 (2016), 67–80.
17. 17 Liu, W., Pfister, E.L., Kennington, L.A., Chase, K.O., Mueller, C., DiFiglia, M., Aronin, N., Does the mutant CAG expansion in huntingtin mRNA interfere with exonucleolytic cleavage of its first exon?. J. Huntingtons Dis. 5 (2016), 33–38.
18. 18 DiFiglia, M., Sena-Esteves, M., Chase, K., Sapp, E., Pfister, E., Sass, M., Yoder, J., Reeves, P., Pandey, R.K., Rajeev, K.G., et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl. Acad. Sci. U S A 104 (2007), 17204–17209.
19. 19 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. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum. Mol. Genet. 12 (2003), 1555–1567.
20. 20 Silva, J.M., Li, M.Z., Chang, K., Ge, W., Golding, M.C., Rickles, R.J., Siolas, D., Hu, G., Paddison, P.J., Schlabach, M.R., et al. Second-generation shRNA libraries covering the mouse and human genomes. Nat. Genet. 37 (2005), 1281–1288.
21. 21 Franciosi, S., Ryu, J.K., Shim, Y., Hill, A., Connolly, C., Hayden, M.R., McLarnon, J.G., Leavitt, B.R., Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease. Neurobiol. Dis. 45 (2012), 438–449.
22. 22 Johnson, E., Chase, K., McGowan, S., Mondo, E., Pfister, E., Mick, E., Friedline, R.H., Kim, J.K., Sapp, E., DiFiglia, M., Aronin, N., Safety of striatal infusion of siRNA in a transgenic Huntington's disease mouse model. J. Huntingtons Dis. 4 (2015), 219–229.
23. 23 Keeler, A.M., Sapp, E., Chase, K., Sottosanti, E., Danielson, E., Pfister, E., Stoica, L., DiFiglia, M., Aronin, N., Sena-Esteves, M., Cellular analysis of silencing the Huntington's disease gene using AAV9 mediated delivery of artificial micro RNA into the striatum of Q140/Q140 mice. J. Huntingtons Dis. 5 (2016), 239–248.
24. 24 Monteys, A.M., Spengler, R.M., Dufour, B.D., Wilson, M.S., Oakley, C.K., Sowada, M.J., McBride, J.L., Davidson, B.L., Single nucleotide seed modification restores in vivo tolerability of a toxic artificial miRNA sequence in the mouse brain. Nucleic Acids Res. 42 (2014), 13315–13327.
25. 25 McBride, J.L., Pitzer, M.R., Boudreau, R.L., Dufour, B., Hobbs, T., Ojeda, S.R., Davidson, B.L., Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Mol. Ther. 19 (2011), 2152–2162.
26. 26 Borel, F., Gernoux, G., Cardozo, B., Metterville, J.P., Toro Cabreja, G.C., Song, L., Su, Q., Gao, G.P., Elmallah, M.K., Brown, R.H. Jr., Mueller, C., Therapeutic rAAVrh10 Mediated SOD1 silencing in adult SOD1(G93A) mice and nonhuman primates. Hum. Gene Ther. 27 (2016), 19–31.
27. 27 Galka-Marciniak, P., Olejniczak, M., Starega-Roslan, J., Szczesniak, M.W., Makalowska, I., Krzyzosiak, W.J., siRNA release from pri-miRNA scaffolds is controlled by the sequence and structure of RNA. Biochim. Biophys. Acta 1859 (2016), 639–649.
28. 28 Fang, W., Bartel, D.P., The menu of features that define primary microRNAs and enable de novo design of microRNA genes. Mol. Cell 60 (2015), 131–145.
29. 29 Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25 (2001), 402–408.
30. 30 Mueller, C., Ratner, D., Zhong, L., Esteves-Sena, M., Gao, G., Production and discovery of novel recombinant adeno-associated viral vectors. Curr. Protoc. Microbiol., Chapter 14, 2012 Unit14D.1.
31. 31 Langmead, B., Trapnell, C., Pop, M., Salzberg, S.L., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol., 10, 2009, R25.
32. 32 Robinson, M.D., McCarthy, D.J., Smyth, G.K., edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 (2010), 139–140.
33. 33 Edgar, R., Domrachev, M., Lash, A.E., Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30 (2002), 207–210.
34. 34 Zhang, Z., Theurkauf, W.E., Weng, Z., Zamore, P.D., Strand-specific libraries for high throughput RNA sequencing (RNA-Seq) prepared without poly(A) selection. Silence, 3, 2012, 9.
35. 35 Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., Salzberg, S.L., TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol., 14, 2013, R36.
36. 36 Love, M.I., Huber, W., Anders, S., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 2014, 550.