Virus-mediated Gene Delivery to Neuronal Progenitors

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

Virus-mediated gene delivery is a very powerful tool for the treatment of inherited disorders (Bjorklund et al., 2000; Dejneka and Bennett, 2001; Manfredsson et al., 2006). Degenerations due to recessive mutations can be slowed or prevented by gene augmentation in which the wild-type form of the transgene of interest is packaged into a recombinant virus. Neurotrophic or neuroprotective factors can be delivered to tissues of interest by transduction with an appropriate virus. And, in the case of dominant inherited degenerations, a recombinant virus carrying siRNA specific to the mutant transgene could be introduced to the cells of interest to result in decreased production of the dominant negative form of the protein.


Gene Delivery Recombinant Virus Retinal Degeneration Fetal Alcohol Syndrome Neuronal Progenitor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahigren S.C., Thakur V., and Bronner-Fraser M., 2002, Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure, Proc Natl Acad Sci. USA 99:10476.CrossRefGoogle Scholar
  2. Auricchio A., Kobinger G., Anand V., Hildinger M., O’Connor E., Maguire A.M., Wilson J.M., and Bennett J., 2001, Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model, Hum Mol Genet. 10:3075.PubMedCrossRefGoogle Scholar
  3. Bedrosian J.C., Gratton M.A., Brigande J.V., Tang W., Landau J., and Bennett J., 2006, In vivo delivery of recombinant viruses to the fetal murine cochlea: Transduction characteristics and long-term effects on auditory function, Mol Ther. 14:328.PubMedCrossRefGoogle Scholar
  4. Bennett J., Wilson J., Sun D., Forbes B., and Maguire A., 1994, Adenovirus vector-mediated in vivo gene transfer into adult murine retina, Invest Ophthalmol Vis Sci. 35:2535.PubMedGoogle Scholar
  5. Bjorklund A., Kirik D., Rosenblad C., Georgievska B., Lundberg C., and Mandel R.J., 2000, Towards a neuroprotective gene therapy for Parkinson’s disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model, Brain Res. 886:82.PubMedCrossRefGoogle Scholar
  6. Bowers W.J., Mastrangelo M.A., Howard D.F., Southerland H.A., Maguire-Zeiss K.A., and Federoff H.J., 2006, Neuronal precursor-restricted transduction via in utero CNS gene delivery of a novel bipartite HSV amplicon/transposase hybrid vector, Mol Ther. 13:580.PubMedCrossRefGoogle Scholar
  7. Dejneka N.S., and Bennett J., 2001, Gene therapy and retinitis pigmentosa: advances and future challenges, Bioessays 23:662.PubMedCrossRefGoogle Scholar
  8. Dejneka N.S., Surace E.M., Aleman T.S., Cideciyan A.V., Lyubarsky A., Savchenko A., Redmond T.M., Tang W., Wei Z., Rex T.S., Glover E., Maguire A.M., Pugh Jr. E.N., Jacobson S.G., and Bennett J., 2004, In utero gene therapy rescues vision in a murine model of congenital blindness, Mol Ther. 9:182.PubMedCrossRefGoogle Scholar
  9. Fields-Berry S.C., Halliday A.L., and Cepko C.L., 1992, A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina, Proc Natl Acad Sci. USA 89:693.PubMedCrossRefGoogle Scholar
  10. Fields P.A., Armstrong E., Hagstrom J.N., Arruda V.R., Murphy M.L., Farrell J.P., High K.A., and Herzog R.W., 2001, Intravenous administration of an E1/E3-deleted adenoviral vector induces tolerance to factor IX in C57BL/6 mice, Gene Ther. 8:354.PubMedCrossRefGoogle Scholar
  11. Jerebtsova M., Batshaw M.L., and Ye X., 2002, Humoral immune response to recombinant adenovirus and adeno-associated virus after in utero administration of viral vectors in mice, Ped Res. 52:95.CrossRefGoogle Scholar
  12. Li T., Adamian M., Roof D.J., Berson E.L., Dryja T.P., Roessler B.J., and Davidson B.L., 1994, In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector, Invest Ophthalmol Vis Sci. 35:2543.PubMedGoogle Scholar
  13. Lipshutz G.S., Flebbe-Rehwaldt L., and Gaensler K.M.L., 2000, Reexpression following readministration of an adenoviral vector in adult mice after initial in utero adenoviral administration, Mol Ther. 2:374.PubMedCrossRefGoogle Scholar
  14. Manfredsson F.P., Lewin A.S., and Mandel R.J., 2006, RNA knockdown as a potential therapeutic strategy in Parkinson’s disease, Gene Ther. 13:517.PubMedCrossRefGoogle Scholar
  15. Manno C.S., Pierce G.F., Arruda V.R., Glader B., Ragni M., Rasko J.J.E., Ozelo M.C., Hoots K., Blatt P., Konkle B., Dake M., Kaye R., Razavi M., Zajko A., Zehnder J., Rustagi P., Nakai H., Chew A., Leonard D., Wright J.F., Lessard R.R., Sommer J.M., Tigges M., Sabatino D., Luk A., Jiang H., Mingozzi F., Couto L., Ertl H.C., High K.A., and Kay M.A., 2006, Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response, Nat Med. 12:342.PubMedCrossRefGoogle Scholar
  16. Pfeifer A., Ikawa M., Dayn Y., and Verma I.M., 2002, Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos. Proc Natl Acad Sci. USA 99:2140.PubMedCrossRefGoogle Scholar
  17. Rex T.S., Peet J.A., Surace E.M., Calvert P.D., Nikonov S.S., Lyubarsky A.L., Bendo E., Hughes T., Pugh Jr. E.N., and Bennett J., 2005, The distribution, concentration, and toxicity of enhanced green fluorescent protein in retinal cells after genomic or somatic (virus-mediated) gene transfer, Mol Vis. 11:1236.PubMedGoogle Scholar
  18. Schneider H., Muhle C., Douar A.M., Waddington S., Jiang Q-J., von der Mark K., Coutelle C., and Rascher W., 2002, Sustained delivery of therapeutic concentrations of human clotting factor IX – a comparison of adenoviral and AAV vectors administered in utero, J Gene Med. 4:46.PubMedCrossRefGoogle Scholar
  19. Seppen J., van Til N.P., van der Rijt R., Hiralall J.K., Kunne C., and Oude Elferink R.P.J., 2006, Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats, Gene Ther. 13:672.PubMedCrossRefGoogle Scholar
  20. Stott S.R.W., and Kirik D., 2006, Targeted in utero delivery of a retroviral vector for gene transfer in the rodent brain, Eur J Neurosci. 24:1897.PubMedCrossRefGoogle Scholar
  21. Surace E.M., Auricchio A., Reich S.J., Rex T., Glover E., Pineles S., Tang W., O’Connor E., Lyubarsky A., Savchenko A., Pugh, Jr. E.N., Maguire A.M., Wilson J.M., and Bennett J., 2003, Delivery of adeno- associated virus vectors to the fetal retina: impact of viral capsid proteins on retinal neuronal progenitor transduction, J Virol. 77:7957.PubMedCrossRefGoogle Scholar
  22. Thakur A., Lansford R., Thakur V., Narone J.N., Atkinson J.B., Buchmiller-Crair T., and Fraser S.E., 2001, Gene transfer to the embryo: strategies for the delivery and expression of proteins at 48 to 56 hours postfertilization, J Ped Surg. 36:1304.CrossRefGoogle Scholar
  23. Turner D.L., Snyder E.Y., and Cepko C.L., 1990, Lineage-independent determination of cell type in the embryonic mouse retina, Neuron 4:833.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations