Advertisement

Design of Muscle Gene Therapy Expression Cassette

  • Yi LaiEmail author
  • Dongsheng Duan
Chapter

Abstract

The first gene therapy drug approved by the European Regulatory Commission involves the transfer of a therapeutic gene to the muscle by adeno-associated viral vector (AAV). Now, muscle gene transfer is quickly becoming a therapy of choice for muscle and non-muscle diseases. Successful muscle gene therapy requires efficient expression of therapeutic proteins in the muscle without causing any toxicity and side effects. To achieve this, the expression cassette of therapeutic proteins needs to be designed rationally. A typical expression cassette usually contains a promoter to initiate transcription, the coding sequence of a transgene, and a termination signal to terminate transcription. Other cis-regulatory elements can be added into the 5′- and 3′-untranslated regions. In this chapter, we review the development of the components of the expression cassette in the context of muscle gene therapy.

Keywords

Muscle Gene therapy Promoter Transgene Termination signal AAV 

References

  1. 1.
    Kastelein JJ, Ross CJ, Hayden MR (2013) From mutation identification to therapy: discovery and origins of the first approved gene therapy in the western world. Hum Gene Ther 24(5):472–478PubMedCrossRefGoogle Scholar
  2. 2.
    Zelenin AV, Kolesnikov VA, Tarasenko OA, Shafei RA, Zelenina IA, Mikhailov VV, Semenova ML, Kovalenko DV, Artemyeva OV, Ivaschenko TE, Evgrafov OV, Dickson G, Baranovand VS (1997) Bacterial beta-galactosidase and human dystrophin genes are expressed in mouse skeletal muscle fibers after ballistic transfection. FEBS Lett 414(2):319–322PubMedCrossRefGoogle Scholar
  3. 3.
    Yue Y, Dongsheng D (2002) Development of multiple cloning site cis-vectors for recombinant adeno-associated virus production. BioTechniques 33(3):672–678PubMedCrossRefGoogle Scholar
  4. 4.
    Qiao C, Li C, Zhao C, Li J, Bian T, Grieger J, Li J, Samulski RJ, Xiao X (2013) K137R mutation on AAV capsid had minimal effect to enhance gene delivery in vivo. Hum Gene Ther Methods 25(1):33–39PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Winbanks CE, Beyer C, Qian H, Gregorevic P (2012) Transduction of skeletal muscles with common reporter genes can promote muscle fiber degeneration and inflammation. PLoS One 7(12):e51627PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Schinkel S, Bauer R, Bekeredjian R, Stucka R, Rutschow D, Lochmuller H, Kleinschmidt JA, Katus HA, Muller OJ (2012) Long-term preservation of cardiac structure and function after AAV9-mediated microdystrophin gene transfer in mdx mice. Hum Gene Ther 23(6):566–575PubMedCrossRefGoogle Scholar
  7. 7.
    Acsadi G, Lochmuller H, Jani A, Huard J, Massie B, Prescott S, Simoneau M, Petrof BJ, Karpati G (1996) Dystrophin expression in muscles of mdx mice after adenovirus-mediated in vivo gene transfer. Hum Gene Ther 7(2):129–140PubMedCrossRefGoogle Scholar
  8. 8.
    Gilbert R, Nalbantoglu J, Howell JM, Davies L, Fletcher S, Amalfitano A, Petrof BJ, Kamen A, Massie B, Karpati G (2001) Dystrophin expression in muscle following gene transfer with a fully deleted (“gutted”) adenovirus is markedly improved by trans-acting adenoviral gene products. Hum Gene Ther 12(14):1741–1755PubMedCrossRefGoogle Scholar
  9. 9.
    Liu M, Yue Y, Harper SQ, Grange RW, Chamberlain JS, Duan D (2005) Adeno-associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury. Mol Ther 11(2):245–256PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Yue Y, Ghosh A, Long C, Bostick B, Smith BF, Kornegay JN, Duan D (2008) A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs. Mol Ther 16(12):1944–1952PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Kornegay JN, Li J, Bogan JR, Bogan DJ, Chen C, Zheng H, Wang B, Qiao C, Howard JFJ, Xiao X (2010) Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. Mol Ther 18(8):1501–1508PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Shin JH, Pan X, Hakim CH, Yang HT, Yue Y, Zhang K, Terjung RL, Duan D (2013) Microdystrophin ameliorates muscular dystrophy in the canine model of duchenne muscular dystrophy. Mol Ther 21(4):750–757PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Yue Y, Pan X, Hakim CH, Kodippili K, Zhang K, Shin JH, Yang HT, McDonald T, Duan D (2015) Safe and bodywide muscle transduction in young adult duchenne muscular dystrophy dogs with adeno-associated virus. Hum Mol Genet 24(20):5880–5890PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Rodino-Klapac LR, Lee JS, Mulligan RC, Clark KR, Mendell JR (2008) Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology 71(4):240–247PubMedCrossRefGoogle Scholar
  15. 15.
    Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK (2015) A phase I/IIa follistatin gene therapy trial for becker muscular dystrophy. Mol Ther 23(1):192–201PubMedCrossRefGoogle Scholar
  16. 16.
    Mendell JR, Sahenk Z, Al-Zaidy S, Rodino-Klapac LR, Lowes LP, Alfano LN, Berry K, Miller N, Yalvac M, Dvorchik I, Moore-Clingenpeel M, Flanigan KM, Church K, Shontz K, Curry C, Lewis S, McColly M, Hogan MJ, Kaspar BK (2017) Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Mol Ther 25(4):870–879PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Bostick B, Ghosh A, Yue Y, Long C, Duan D (2007) Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration. Gene Ther 14(22):1605–1609PubMedCrossRefGoogle Scholar
  18. 18.
    Inagaki K, Fuess S, Storm TA, Gibson GA, Mctiernan CF, Kay MA, Nakai H (2006) Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Mol Ther 14(1):45–53PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Wang Z, Zhu T, Qiao C, Zhou L, Wang B, Zhang J, Chen C, Li J, Xiao X (2005) Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 23(3):321–328PubMedCrossRefGoogle Scholar
  20. 20.
    Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK (2009) Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 27(1):59–65PubMedCrossRefGoogle Scholar
  21. 21.
    Zincarelli C, Soltys S, Rengo G, Rabinowitz JE (2008) Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 16(6):1073–1080PubMedCrossRefGoogle Scholar
  22. 22.
    Brooks AR, Harkins RN, Wang P, Qian HS, Liu P, Rubanyi GM (2004) Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle. J Gene Med 6(4):395–404PubMedCrossRefGoogle Scholar
  23. 23.
    Leger A, Le Guiner C, Nickerson ML, McGee Im K, Ferry N, Moullier P, Snyder RO, Penaud-Budloo M (2011) Adeno-associated viral vector-mediated transgene expression is independent of DNA methylation in primate liver and skeletal muscle. PLoS One 6(6):e20881PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Challita PM, Kohn DB (1994) Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo. Proc Natl Acad Sci U S A 91(7):2567–2571PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Palmer TD, Rosman GJ, Osborne WR, Miller AD (1991) Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci U S A 88(4):1330–1334PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Scharfmann R, Axelrod JH, Verma IM (1991) Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. Proc Natl Acad Sci U S A 88(11):4626–4630PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Qin JY, Zhang L, Clift KL, Hulur I, Xiang AP, Ren BZ, Lahn BT (2010) Systematic comparison of constitutive promoters and the doxycycline-inducible promoter. PLoS One 5:e10611PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Post H, Kajstura J, Lei B, Sessa WC, Byrne B, Anversa P, Hintze TH, Recchia FA (2003) Adeno-associated virus mediated gene delivery into coronary microvessels of chronically instrumented dogs. J Appl Physiol 95(4):1688–1694PubMedCrossRefGoogle Scholar
  29. 29.
    Li X, Eastman EM, Schwartz RJ, Draghia-Akli R (1999) Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences. Nat Biotechnol 17(3):241–245PubMedCrossRefGoogle Scholar
  30. 30.
    Koo T, Malerba A, Athanasopoulos T, Trollet C, Boldrin L, Ferry A, Popplewell L, Foster H, Foster K, Dickson G (2011) Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of alpha1-syntrophin and alpha-dystrobrevin in skeletal muscles of mdx mice. Hum Gene Ther 22(11):1379–1388PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Lai Y, Zhao J, Yue Y, Wasala NB, Duan D (2014) Partial restoration of cardiac function with ΔPDZ nNOS in aged mdx model of duchenne cardiomyopathy. Hum Mol Genet 23(12):3189–3199PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Yue Y, Li Z, Harper SQ, Davisson RL, Chamberlain JS, Duan D (2003) Microdystrophin gene therapy of cardiomyopathy restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart. Circulation 108(13):1626–1632PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Wang B, Li J, Fu FH, Chen C, Zhu X, Zhou L, Jiang X, Xiao X (2008) Construction and analysis of compact muscle-specific promoters for AAV vectors. Gene Ther 15(22):1489–1499PubMedCrossRefGoogle Scholar
  34. 34.
    Katwal AB, Konkalmatt PR, Piras BA, Hazarika S, Li SS, John Lye R, Sanders JM, Ferrante EA, Yan Z, Annex BH, French BA (2013) Adeno-associated virus serotype 9 efficiently targets ischemic skeletal muscle following systemic delivery. Gene Ther 20(9):930–938PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Salva MZ, Himeda CL, Tai PW, Nishiuchi E, Gregorevic P, Allen JM, Finn EE, Nguyen QG, Blankinship MJ, Meuse L, Chamberlain JS, Hauschka SD (2007) Design of tissue-specific regulatory cassettes for high-level rAAV-mediated expression in skeletal and cardiac muscle. Mol Ther 15(2):320–329PubMedCrossRefGoogle Scholar
  36. 36.
    Talbot GE, Waddington SN, Bales O, Tchen RC, Antoniou MN (2010) Desmin-regulated lentiviral vectors for skeletal muscle gene transfer. Mol Ther 18(3):601–608PubMedCrossRefGoogle Scholar
  37. 37.
    Pacak CA, Sakai Y, Thattaliyath BD, Mah CS, Byrne BJ (2008) Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice. Genet Vaccines Ther 6:13PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Prasad KM, Smith RS, Xu Y, French BA (2011) A single direct injection into the left ventricular wall of an AAV9 vector expressing EcSOD from the cardiac troponin-T promoter protects mice against myocardial infarction. J Gene Med 13(6):333–341PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Prasad KM, Xu Y, Yang Z, Acton ST, French BA (2011) Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution. Gene Ther 18(1):43–52PubMedCrossRefGoogle Scholar
  40. 40.
    Konkalmatt PR, Beyers RJ, O’Connor DM, Xu Y, Seaman ME, French BA (2013) Cardiac-selective expression of EcSOD after systemic injection of AAV9 protects the heart against post-MI LV remodeling. Circ Cardiovasc Imaging 6(3):478–486PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Werfel S, Jungmann A, Lehmann L, Ksienzyk J, Bekeredjian R, Kaya Z, Leuchs B, Nordheim A, Backs J, Engelhardt S, Katus HA, Muller OJ (2014) Rapid and highly efficient inducible cardiac gene knockout in adult mice using AAV-mediated expression of Cre recombinase. Cardiovasc Res 104(1):15–23PubMedCrossRefGoogle Scholar
  42. 42.
    Guo Y, VanDusen NJ, Zhang L, Gu W, Sethi I, Guatimosim S, Ma Q, Jardin BD, Ai Y, Zhang D, Chen B, Guo A, Yuan GC, Song LS, Pu WT (2017) Analysis of cardiac myocyte maturation using CASAAV, a platform for rapid dissection of cardiac myocyte gene function in vivo. Circ Res 120(12):1874–1888PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hauser MA, Robinson A, Hartigan-O’Connor D, Williams-Gregory DA, Buskin JN, Apone S, Kirk CJ, Hardy S, Hauschka SD, Chamberlain JS (2000) Analysis of muscle creatine kinase regulatory elements in recombinant adenoviral vectors. Mol Ther 2(1):16–25PubMedCrossRefGoogle Scholar
  44. 44.
    Cordier L, Gao GP, Hack AA, McNally EM, Wilson JM, Chirmule N, Sweeney HL (2001) Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies. Hum Gene Ther 12(2):205–215PubMedCrossRefGoogle Scholar
  45. 45.
    Childers MK, Joubert R, Poulard K, Moal C, Grange RW, Doering JA, Lawlor MW, Rider BE, Jamet T, Daniele N, Martin S, Riviere C, Soker T, Hammer C, Van Wittenberghe L, Lockard M, Guan X, Goddard M, Mitchell E, Barber J, Williams JK, Mack DL, Furth ME, Vignaud A, Masurier C, Mavilio F, Moullier P, Beggs AH, Buj-Bello A (2014) Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med 6(220):220ra10PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Le Guiner C, Servais L, Montus M, Larcher T, Fraysse B, Moullec S, Allais M, François V, Dutilleul M, Malerba A, Koo T, Thibaut JL, Matot B, Devaux M, Le Duff J, Deschamps JY, Barthelemy I, Blot S, Testault I, Wahbi K, Ederhy S, Martin S, Veron P, Georger C, Athanasopoulos T, Masurier C, Mingozzi F, Carlier P, Gjata B, Hogrel JY, Adjali O, Mavilio F, Voit T, Moullier P, Dickson G (2017) Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun 8:16105PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Koo T, Okada T, Athanasopoulos T, Foster H, Takeda S, Dickson G (2011) Long-term functional adeno-associated virus-microdystrophin expression in the dystrophic CXMDj dog. J Gene Med 13(9):497–506PubMedCrossRefGoogle Scholar
  48. 48.
    Pichavant C, Chapdelaine P, Cerri DG, Dominique JC, Quenneville SP, Skuk D, Kornegay JN, Bizario JC, Xiao X, Tremblay JP (2010) Expression of dog microdystrophin in mouse and dog muscles by gene therapy. Mol Ther 18(5):1002–1009PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ma H, Wu Y, Dang Y, Choi JG, Zhang J, Wu H (2014) Pol III promoters to express small RNAs: delineation of transcription initiation. Mol Ther Nucleic Acids 3:e161PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Roelz R, Pilz IH, Mutschler M, Pahl HL (2010) Of mice and men: human RNA polymerase III promoter U6 is more efficient than its murine homologue for shRNA expression from a lentiviral vector in both human and murine progenitor cells. Exp Hematol 38(9):792–797PubMedCrossRefGoogle Scholar
  51. 51.
    Goyenvalle A, Vulin A, Fougerousse F, Leturcq F, Kaplan JC, Garcia L, Danos O (2004) Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306(5702):1796–1799PubMedCrossRefGoogle Scholar
  52. 52.
    Goyenvalle A, Babbs A, Wright J, Wilkins V, Powell D, Garcia L, Davies KE (2012) Rescue of severely affected dystrophin/utrophin-deficient mice through scAAV-U7snRNA-mediated exon skipping. Hum Mol Genet 21(11):2559–2571PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Le Hir M, Goyenvalle A, Peccate C, Precigout G, Davies KE, Voit T, Garcia L, Lorain S (2013) AAV genome loss from dystrophic mouse muscles during AAV-U7 snRNA-mediated exon-skipping therapy. Mol Ther 21(8):1551–1558PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Mayra A, Tomimitsu H, Kubodera T, Kobayashi M, Piao W, Sunaga F, Hirai Y, Shimada T, Mizusawa H, Yokota T (2011) Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles. Biochem Biophys Res Commun 405(2):204–209PubMedCrossRefGoogle Scholar
  55. 55.
    Yang Q, Tang Y, Imbrogno K, Lu A, Proto JD, Chen A, Guo F, Fu FH, Huard J, Wang B (2012) AAV-based shRNA silencing of NF-kappaB ameliorates muscle pathologies in mdx mice. Gene Ther 19(12):1196–1204PubMedCrossRefGoogle Scholar
  56. 56.
    Askou AL, Pournaras JA, Pihlmann M, Svalgaard JD, Arsenijevic Y, Kostic C, Bek T, Dagnaes-Hansen F, Mikkelsen JG, Jensen TG, Corydon TJ (2012) Reduction of choroidal neovascularization in mice by AAV-delivered anti-VEGF shRNA. J Gene Med 14(11):632–641PubMedCrossRefGoogle Scholar
  57. 57.
    Bish LT, Sleeper MM, Reynolds C, Gazzara J, Withnall E, Singletary GE, Buchlis G, Hui D, High KA, Gao G, Wilson JM, Sweeney HL (2011) 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(8):969–977PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Fellmann C, Hoffmann T, Sridhar V, Hopfgartner B, Muhar M, Roth M, Lai DY, Barbosa IA, Kwon JS, Guan Y, Sinha N, Zuber J (2013) An optimized microRNA backbone for effective single-copy RNAi. Cell Rep 5(6):1704–1713PubMedCrossRefGoogle Scholar
  59. 59.
    Vieira NM, Spinazzola JM, Alexander MS, Moreira YB, Kawahara G, Gibbs DE, Mead LC, Verjovski-Almeida S, Zatz M, Kunkel LM (2017) Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 114(23):6080–6085PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Ghahramani Seno MM, Graham IR, Athanasopoulos T, Trollet C, Pohlschmidt M, Crompton MR, Dickson G (2008) RNAi-mediated knockdown of dystrophin expression in adult mice does not lead to overt muscular dystrophy pathology. Hum Mol Genet 17:2622–2632PubMedCrossRefGoogle Scholar
  61. 61.
    Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, Bhattacharyya S, Shelton JM, Bassel-Duby R, Olson EN (2016) Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351(6271):400–403PubMedCrossRefGoogle Scholar
  62. 62.
    Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Rivera RM, Madhavan S, Pan X, Ran FA, Yan WX, Asokan A, Zhang F, Duan D, Gersbach CA (2016) In vivo genome editing improves muscle function in a mouse model of duchenne muscular dystrophy. Science 351(6271):403–407PubMedCrossRefGoogle Scholar
  63. 63.
    Tabebordbar M, Zhu K, Cheng JK, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran FA, Cong L, Zhang F, Vandenberghe LH, Church GM, Wagers AJ (2016) In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 351(6271):407–411PubMedCrossRefGoogle Scholar
  64. 64.
    Bengtsson NE, Hall JK, Odom GL, Phelps MP, Andrus CR, Hawkins RD, Hauschka SD, Chamberlain JR, Chamberlain JS (2017) Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy. Nat Commun 8:14454PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kim E, Koo T, Park SW, Kim D, Kim K, Cho HY, Song DW, Lee KJ, Jung MH, Kim S, Kim JH, Kim JH, Kim JS (2017) In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat Commun 8:14500PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    El Refaey M, Xu L, Gao Y, Canan BD, Adesanya TA, Warner SC, Akagi K, Symer DE, Mohler PJ, Ma J, Janssen PM, Han R (2017) In vivo genome editing restores dystrophin expression and cardiac function in dystrophic mice. Circ Res 121(8):923–929PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Kemaladewi DU, Maino E, Hyatt E, Hou H, Ding M, Place KM, Zhu X, Bassi P, Baghestani Z, Deshwar AG, Merico D, Xiong HY, Frey BJ, Wilson MD, Ivakine EA, Cohn RD (2017) Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism. Nat Med 23(8):984–989PubMedCrossRefGoogle Scholar
  68. 68.
    Cao L, Lin EJ, Cahill MC, Wang C, Liu X, During MJ (2009) Molecular therapy of obesity and diabetes by a physiological autoregulatory approach. Nat Med 15(4):447–454PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Porro F, Bortolussi G, Barzel A, De Caneva A, Iaconcig A, Vodret S, Zentilin L, Kay MA, Muro AF (2017) Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model. EMBO Mol Med 9(10):1346–1355PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM, Kay MA (2015) Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517(7534):360–364PubMedCrossRefGoogle Scholar
  71. 71.
    Arimbasseri AG, Rijal K, Maraia RJ (2013) Transcription termination by the eukaryotic RNA polymerase III. Biochim Biophys Acta 1829(3–4):318–330PubMedCrossRefGoogle Scholar
  72. 72.
    Hager S, Frame FM, Collins AT, Burns JE, Maitland NJ (2008) An internal polyadenylation signal substantially increases expression levels of lentivirus-delivered transgenes but has the potential to reduce viral titer in a promoter-dependent manner. Hum Gene Ther 19(8):840–850PubMedCrossRefGoogle Scholar
  73. 73.
    Choi JH, Yu NK, Baek GC, Bakes J, Seo D, Nam HJ, Baek SH, Lim CS, Lee YS, Kaang BK (2014) Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons. Mol Brain 7:17PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ostedgaard LS, Rokhlina T, Karp PH, Lashmit P, Afione S, Schmidt M, Zabner J, Stinski MF, Chiorini JA, Welsh MJ (2005) A shortened adeno-associated virus expression cassette for CFTR gene transfer to cystic fibrosis airway epithelia. Proc Natl Acad Sci U S A 102(8):2952–2957PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Powell SK, Rivera-Soto R, Gray SJ (2015) Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy. Discov Med 19(102):49–57PubMedPubMedCentralGoogle Scholar
  76. 76.
    Levitt N, Briggs D, Gil A, Proudfoot NJ (1989) Definition of an efficient synthetic poly(A) site. Genes Dev 3(7):1019–1025PubMedCrossRefGoogle Scholar
  77. 77.
    Proudfoot NJ (2011) Ending the message: poly(A) signals then and now. Genes Dev 25(17):1770–1782PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Schambach A, Galla M, Maetzig T, Loew R, Baum C (2007) Improving transcriptional termination of self-inactivating gamma-retroviral and lentiviral vectors. Mol Ther 15(6):1167–1173PubMedCrossRefGoogle Scholar
  79. 79.
    Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Rustagi PK, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 12(3):342–347PubMedCrossRefGoogle Scholar
  80. 80.
    Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000) Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 24(3):257–261PubMedCrossRefGoogle Scholar
  81. 81.
    Wu Z, Sun J, Zhang T, Yin C, Yin F, Van Dyke T, Samulski RJ, Monahan PE (2008) Optimization of self-complementary AAV vectors for liver-directed expression results in sustained correction of hemophilia B at low vector dose. Mol Ther 16(2):280–289PubMedCrossRefGoogle Scholar
  82. 82.
    Lu J, Williams JA, Luke J, Zhang F, Chu K, Kay MA (2017) A 5’non-coding exon containing engineered intron enhances transgene expression from recombinant AAV vectors in vivo. Hum Gene Ther 28(1):125–134PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Bell P, Wang L, Chen S-J, Yu H, Zhu Y, Nayal M, He Z, White J, Lebel-Hagan D, Wilson JM (2016) Effects of self-complementarity, codon optimization, transgene, and dose on liver transduction with AAV8. Hum Gene Ther Methods 27(6):228–237PubMedCrossRefGoogle Scholar
  84. 84.
    Foster H, Sharp PS, Athanasopoulos T, Trollet C, Graham IR, Foster K, Wells DJ, Dickson G (2008) Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer. Mol Ther 16(11):1825–1832PubMedCrossRefGoogle Scholar
  85. 85.
    Athanasopoulos T, Foster H, Foster K, Dickson G (2011) Codon optimization of the microdystrophin gene for duchene muscular dystrophy gene therapy. Methods Mol Biol 709:21–37PubMedCrossRefGoogle Scholar
  86. 86.
    Kudla G, Lipinski L, Caffin F, Helwak A, Zylicz M (2006) High guanine and cytosine content increases mRNA levels in mammalian cells. PLoS Biol 4(6):e180PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Faust SM, Bell P, Cutler BJ, Ashley SN, Zhu Y, Rabinowitz JE, Wilson JM (2013) CpG-depleted adeno-associated virus vectors evade immune detection. J Clin Invest 123(7):2994–3001PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Brown BD, Venneri MA, Zingale A, Sergi Sergi L, Naldini L (2006) Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Nat Med 12(5):585–591PubMedCrossRefGoogle Scholar
  89. 89.
    Brown BD, Gentner B, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L (2007) Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol 25(12):1457–1467PubMedCrossRefGoogle Scholar
  90. 90.
    Cawood R, Chen HH, Carroll F, Bazan-Peregrino M, van Rooijen N, Seymour LW (2009) Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells. PLoS Pathog 5(5):e1000440PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Kelly EJ, Hadac EM, Greiner S, Russell SJ (2008) Engineering microRNA responsiveness to decrease virus pathogenicity. Nat Med 14(11):1278–1283PubMedCrossRefGoogle Scholar
  92. 92.
    Geisler A, Schon C, Grossl T, Pinkert S, Stein EA, Kurreck J, Vetter R, Fechner H (2013) Application of mutated miR-206 target sites enables skeletal muscle-specific silencing of transgene expression of cardiotropic AAV9 vectors. Mol Ther 21(5):924–933PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Qiao C, Yuan Z, Li J, He B, Zheng H, Mayer C, Li J, Xiao X (2011) Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther 18(4):403–410PubMedCrossRefGoogle Scholar
  94. 94.
    Majowicz A, Maczuga P, Kwikkers KL, van der Marel S, van Logtenstein R, Petry H, van Deventer SJ, Konstantinova P, Ferreira V (2013) Mir-142-3p target sequences reduce transgene directed immunogenicity following intramuscular AAV1 vector-mediated gene delivery. J Gene Med 15(6–7):219–232PubMedCrossRefGoogle Scholar
  95. 95.
    Mattar CN, Wong AM, Hoefer K, Alonso-Ferrero ME, Buckley SM, Howe SJ, Cooper JD, Waddington SN, Chan JK, Rahim AA (2015) Systemic gene delivery following intravenous administration of AAV9 to fetal and neonatal mice and late-gestation nonhuman primates. FASEB J 29(9):3876–3888PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Wang L, Louboutin JP, Bell P, Greig J, Li Y, Wu D, Wilson JM (2011) Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors. J Thromb Haemost 9(10):2009–2019PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    O’Rourke JP, Hiraragi H, Urban K, Patel M, Olsen JC, Bunnell BA (2003) Analysis of gene transfer and expression in skeletal muscle using enhanced EIAV lentivirus vectors. Mol Ther 7(5. Pt 1):632–639PubMedCrossRefGoogle Scholar
  98. 98.
    Foster K, Foster H, Dickson JG (2006) Gene therapy progress and prospects: duchenne muscular dystrophy. Gene Ther 13(24):1677–1685PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Molecular Microbiology and Immunology, School of MedicineUniversity of MissouriColumbiaUSA
  2. 2.Department of Neurology, School of MedicineUniversity of MissouriColumbiaUSA
  3. 3.Department of Biomedical Sciences, College of Veterinary MedicineUniversity of MissouriColumbiaUSA
  4. 4.Department of BioengineeringUniversity of MissouriColumbiaUSA

Personalised recommendations