Neuronal Specificity of HSV/sleeping Beauty Amplicon Transduction in Utero is Driven Primarily by Tropism and Cell Type Composition

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2007 Jul 27

PMID 17653102

Citations 9

Authors

Elise B Peterson

Michael A Mastrangelo

Howard J Federoff

William J Bowers

Affiliations

Soon will be listed here.

Abstract

A novel bipartite vector system consisting of the herpes simplex virus (HSV) amplicon and the Sleeping Beauty(SB) transposon was previously shown to efficiently deliver a "transgenon" (integrating transgene) in utero. This vector platform facilitated long-term transgenon expression specifically within neurons and neuronal precursor cells of the rodent brain. However, the mechanism underlying the neurospecificity of the HSV/SB amplicon in the setting of mouse embryogenesis is unknown. We find that embryonic cells expressing the Sox1 "neurocompetence" transcription factor represent the primary targets for HSV amplicon transduction in utero. These cells, which comprise the ependymal and subventricular zones (SVZs), express significant levels of high-mobility-group protein B1 (HMGB1), a co-factor shown to facilitate SB-mediated transposition. Using a conventional, non-integrating amplicon expressing Cre recombinase to "tag" transduced cells embryonically in ROSA26 Cre indicator mice in utero, we found transduced cells were exclusively of the neuronal lineage but that in comparison to HSV/SB-mediated in utero delivery, staining patterns were less widespread and "tagged" neuroprogenitor cells were absent. Our findings demonstrate that in utero HSV/SB amplicon gene transfer is primarily neurospecific owing to viral tropism and target cell populations present embryonically, where multi-potent cells of the developing embryo are supportive of SB-driven transposition.

Citing Articles

HMGB1 in health and disease.

Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L Mol Aspects Med. 2014; 40:1-116.

PMID: 25010388 PMC: 4254084. DOI: 10.1016/j.mam.2014.05.001.

Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.

de Silva S, Bowers W Curr Gene Ther. 2011; 11(5):332-40.

PMID: 21711226 PMC: 4141986. DOI: 10.2174/156652311797415845.

Comparative genomic integration profiling of Sleeping Beauty transposons mobilized with high efficacy from integrase-defective lentiviral vectors in primary human cells.

Moldt B, Miskey C, Staunstrup N, Gogol-Doring A, Bak R, Sharma N Mol Ther. 2011; 19(8):1499-510.

PMID: 21468003 PMC: 3149173. DOI: 10.1038/mt.2011.47.

Early oligodendrocyte/myelin pathology in Alzheimer's disease mice constitutes a novel therapeutic target.

Desai M, Mastrangelo M, Ryan D, Sudol K, Narrow W, Bowers W Am J Pathol. 2010; 177(3):1422-35.

PMID: 20696774 PMC: 2928974. DOI: 10.2353/ajpath.2010.100087.

Virion-associated cofactor high-mobility group DNA-binding protein-1 facilitates transposition from the herpes simplex virus/Sleeping Beauty amplicon vector platform.

de Silva S, Lotta Jr L, Burris C, Bowers W Hum Gene Ther. 2010; 21(11):1615-22.

PMID: 20568967 PMC: 2978546. DOI: 10.1089/hum.2010.022.

References

Kishi M, Mizuseki K, Sasai N, Yamazaki H, Shiota K, Nakanishi S . Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. Development. 2000; 127(4):791-800. DOI: 10.1242/dev.127.4.791. View

Koizumi H, Higginbotham H, Poon T, Tanaka T, Brinkman B, Gleeson J . Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Nat Neurosci. 2006; 9(6):779-86. DOI: 10.1038/nn1704. View

Bowers W, Howard D, Brooks A, Halterman M, Federoff H . Expression of vhs and VP16 during HSV-1 helper virus-free amplicon packaging enhances titers. Gene Ther. 2001; 8(2):111-20. DOI: 10.1038/sj.gt.3301340. View

Zayed H, Izsvak Z, Khare D, Heinemann U, Ivics Z . The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition. Nucleic Acids Res. 2003; 31(9):2313-22. PMC: 154227. DOI: 10.1093/nar/gkg341. View

Bowers W, Olschowka J, Federoff H . Immune responses to replication-defective HSV-1 type vectors within the CNS: implications for gene therapy. Gene Ther. 2003; 10(11):941-5. DOI: 10.1038/sj.gt.3302047. View

Kan L, Israsena N, Zhang Z, Hu M, Zhao L, Jalali A . Sox1 acts through multiple independent pathways to promote neurogenesis. Dev Biol. 2004; 269(2):580-94. DOI: 10.1016/j.ydbio.2004.02.005. View

Oehmig A, Fraefel C, Breakefield X . Update on herpesvirus amplicon vectors. Mol Ther. 2004; 10(4):630-43. DOI: 10.1016/j.ymthe.2004.06.641. View

Geller A, Breakefield X . A defective HSV-1 vector expresses Escherichia coli beta-galactosidase in cultured peripheral neurons. Science. 1988; 241(4873):1667-9. PMC: 2581874. DOI: 10.1126/science.241.4873.1667. View

Jin B, Belloni M, Conti B, Federoff H, Starr R, Son J . Prolonged in vivo gene expression driven by a tyrosine hydroxylase promoter in a defective herpes simplex virus amplicon vector. Hum Gene Ther. 1996; 7(16):2015-24. DOI: 10.1089/hum.1996.7.16-2015. View

10.

Brooks A, Muhkerjee B, Panahian N, Cory-Slechta D, Federoff H . Nerve growth factor somatic mosaicism produced by herpes virus-directed expression of cre recombinase. Nat Biotechnol. 1997; 15(1):57-62. DOI: 10.1038/nbt0197-57. View

11.

Pevny L, Sockanathan S, Placzek M, Lovell-Badge R . A role for SOX1 in neural determination. Development. 1998; 125(10):1967-78. DOI: 10.1242/dev.125.10.1967. View

12.

Hatten M . Central nervous system neuronal migration. Annu Rev Neurosci. 1999; 22:511-39. DOI: 10.1146/annurev.neuro.22.1.511. View

13.

Bustin M . Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol. 1999; 19(8):5237-46. PMC: 84367. DOI: 10.1128/MCB.19.8.5237. View

14.

Zhao S, Nichols J, Smith A, Li M . SoxB transcription factors specify neuroectodermal lineage choice in ES cells. Mol Cell Neurosci. 2004; 27(3):332-42. DOI: 10.1016/j.mcn.2004.08.002. View

15.

Stein C, Martins I, Davidson B . The lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain. Mol Ther. 2005; 11(3):382-9. DOI: 10.1016/j.ymthe.2004.11.008. View

16.

Wegner M, Stolt C . From stem cells to neurons and glia: a Soxist's view of neural development. Trends Neurosci. 2005; 28(11):583-8. DOI: 10.1016/j.tins.2005.08.008. View

17.

Karram K, Chatterjee N, Trotter J . NG2-expressing cells in the nervous system: role of the proteoglycan in migration and glial-neuron interaction. J Anat. 2005; 207(6):735-44. PMC: 1571586. DOI: 10.1111/j.1469-7580.2005.00461.x. View

18.

Bowers W, Mastrangelo M, Howard D, Southerland H, Maguire-Zeiss K, Federoff H . Neuronal precursor-restricted transduction via in utero CNS gene delivery of a novel bipartite HSV amplicon/transposase hybrid vector. Mol Ther. 2006; 13(3):580-8. DOI: 10.1016/j.ymthe.2005.11.011. View

19.

Suzuki M, Kasai K, Saeki Y . Plasmid DNA sequences present in conventional herpes simplex virus amplicon vectors cause rapid transgene silencing by forming inactive chromatin. J Virol. 2006; 80(7):3293-300. PMC: 1440389. DOI: 10.1128/JVI.80.7.3293-3300.2006. View

20.

Walisko O, Izsvak Z, Szabo K, Kaufman C, Herold S, Ivics Z . Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1. Proc Natl Acad Sci U S A. 2006; 103(11):4062-7. PMC: 1449646. DOI: 10.1073/pnas.0507683103. View