Abstract
Several years ago it was reported that the entry of adenovirus particles could augment the uptake of polylysine-condensed DNA molecules (Curiel et al. 1991), a phenomenon similar to previously described adenovirus augmentation of both fluid phase markers and receptor-bound molecules (Fernández-Puentes and Carrasco 1980; Fitzgerald et al. 1983). This use of adenovirus to enhance gene delivery has proven to be a fruitful approach. A number of reviews of the general properties of this system have recently been published (Curiel 1993; Cotten and Wagner 1993; Wagner et al. 1994). In this review I will provide a summary of the current methods of generating adenovirus-DNA transfection complexes as well as discussing two of the toxicity problems that we have encountered with this system and describing some solutions to these problems. The first problem encountered was due to virus gene expression and leakiness in the replication defect of the commonly used defective adenovirus strains. This problem was solved by developing a psoralen inactivation method that inactivates the virus DNA and blocks viral gene expression and replication without impairing the entry functions of the virus (Cotten et al. 1994b). The second problem was due to a toxicity generated by cytoplasmic delivery of lipopolysaccharide (LPS, endotoxin) that frequently contaminates bacterial DNA preparations. The LPS problem has been solved by identifying reliable methods of removing LPS from DNA (Cotten et al. 1994a) or by including LPS-binding polymyxin in the transfection medium.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baatz JE, Bruno MD, Ciraolo PJ, Glasser SW, Stripp BR, Smyth KL, Korfhagen TR (1994) Utilization of modified surfactant-associated protein B for delivery of DNA to airway cells in culture. Proc Natl Acad Sci USA 91: 2547–2551
Bai M, Harfe B, Freimuth P (1993) Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell rounding activity and delay virus reproduction in flat cells. J Virol 67: 5198–5205
Belin M.-T, Boulanger P (1993) Involvement of cellular adhesion sequences in the attachment of adenovirus to the HeLa cell surface. J Gen Virol 74: 1485–1497
Berenbaum M, Feeney P (1981) Toxicity of angular furanocoumarins to swallowtail butterflies: escalation in a revolutionary arms race. Science 212: 927–929
Bridge E, Ketner G (1989) Redundant control of adenovirus late gene expression by early region 4. J Virol 63: 631–638
Buschle M, Cotten M, Kirlappos H, Mechtler K, Schaffner G, Zauner W, Bimstiel ML, Wagner E (1995) Receptor-mediated gene transfer into human T-lymphocytes via binding of DNA/CD3 antibody particles to the CD3 T cell receptor complex. Human Gene Therapy (in press)
Chen P, Omelles D, Shenk T (1993) The adenovirus L3 23-kilodalton proteinase cleaves the armino-terminal head domain from cytokeratin 18 and disrupts the cytokeratin network of HeLa cells. J Virol 67: 3507–3514
Cotten M, Wagner E (1993) Non-viral approaches to gene therapy. Curr Opin Biotechnol 4: 705–710
Cotten M, Wagner E, Zatloukal K, Phillips S, Curiel DT, Bimstiel ML, (1992) High-efficiency receptor-mediated delivery of small and large (48kb) gene constructs using the endosome disruption activity of defective or chemically inactivated adenovirus particles. Proc Natl Acad Sci USA 89: 6094–6098
Cotten M, Wagner E, Bimstiel ML (1993a) Receptor-mediated transport of DNA into eukaryotic cells. Methods Enzymol 217: 618–644
Cotten M, Wagner E, Zatloukal K, Bimstiel ML (1993b) Chicken adenovirus (CELO virus) particles augment receptor-mediated DNA delivery to mammalian cells and yield exceptional levels of stable transformants. J Virol 67: 3777–3785
Cotten M, Baker A, Saltik M, Wagner E, Buschle M (1994a) Lipopolysaccharide is a frequent contaminant of plasmid DNA preparations and can be toxic to primary cells in the presence of adenovirus. Gene Ther 1: 239–246
Cotten M, Saltik M, Kursa M, Wagner E, Maass G, Bimstiel M (1994b) Psoralen treatment of adenovirus particles eliminates virus replication and transcription while maintaining the endosomolytic activity of the virus capsid. Virology 205: 254–261
Cristiano RJ, Smith LC, Woo SLC (1993a) Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. Proc Natl Acad Sci USA 90: 2122–2126
Cristiano RJ, Smith LC, Kay MA, Brinkley BR, Woo SLC (1993b) Hepatic gene therapy: efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex. Proc Natl Acad Sci USA 90: 11548–11552
Curiel D (1993) Adenovirus facilitation of molecular conjugate-mediated gene transfer. Prog Med Virol 40: 1–18
Curiel DT, Agarwal S, Wagner E and Cotten M (1991) Adenovirus enhancement of transferring-polylysine mediated gene delivery. Proc Natl Acad Sci USA 88: 8850–8854
Curiel D, Wagner E, Cotten M, Bimstiel ML, Agarwal S, Li C, Loechel S, Hu P (1992) High efficiency gene transfer mediated by adenovirus coupled to DNA polylysine complexes. Hum Gene Ther 3: 147–154
Datta S, Soong C, Wang D, Harter M (1991) A purified adenovirus 289-amino-acid E1A protein activates RNA polymerase III transcription in vitro and alters transcription factor UIC. J Virol 65: 5297–5304
Debbas M, White E (1993) Wild-type p53 mediates apoptosis by E1 A, which is inhibited by E1B. Genes Dev 7: 546–554
Defer C, Belin M.-T, Caillet-Boudin M.-L, Boulanger P (1990) Human adenovirus-host cell interactions: comparitive study with members of subgroup B and C. J Virol 64: 3661–3673
Everett S, Ginsberg HS (1985) A toxin like material separable from type 5 adenovirus particles. Virology 6: 770–771
Fernández-Puentes C, Carrasco L (1980) Viral infection permeabilizes mammalian cells to protein toxins. Cell 20: 769–775
Fisher KJ, Wilson JM (1994) Biochemical and functional analysis of an adenovirus-based ligand complex for gene transfer. Biochem J 299: 49–58
Fitzgerald D, Padmanabhan R, Pastan I, Willingham M (1983) Adenovirus-induced release of epidermal growth factor and Pseudomonas toxin into the cytosol of KB cells during receptor-mediated endocytosis. Cell 32: 607–617
Gooding LR (1992) Virus proteins that counteract host immune defenses. Cell 71: 5–7
Graham F, Smiley J, Russell W, Nairn R (1977) Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36: 59–72
Greber UF, Willetts M, Webster P, Helenius A (1993) Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75: 1–20
Hanson CV (1992) Photochemical inactivation of viruses with psoralens: an overview. Blood Celisi 8: 7–25
Hanson CV, Riggs JL, Lennette EH (1978) Photochemical inactivation of DNA and RNA viruses by psoralen derivatives. J Gen Virol 40: 345–358
Hoeffler WK, Kovelman R, Roeder RG (1988) Activation of transcription factor IIIC by the adenovirus E1A protein. Cell 53: 907–920
Horvath J, Weber J (1988) Nonpermissivity of human peripheral blood lymphocytes to adenovirus type 2 infection. J Virol 62: 341–345
Horvath J, Faxing C, Weber JM (1991) Complementation of adenovirus early region 1a and 2a mutants by Epstein-Barr virus immortalized lymphoblastoid cell lines. Virology 184: 141–148
Ivie GW, Holt DL, Ivey MC (1981) Natural toxicants in human food: psoralens in raw and cooked parsnip root. Science 213: 909–910
Jones N, Shenk T (1979) An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Natl Acad Sci USA 76: 3665–3669
Komhauser A, Warner WG, Giles AL (1982) Psoralen photoxicity: correlation with serum and epidermal 8-methoxypsoralen and 5-methoxypsoralen in the guinea pig. Science 217: 733–735
Lowe SW, Ruley HE (1993) Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev 7: 535–545
Manche L, Green SR, Schmedt C, Mathews MB (1992) Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol Cell Biol 12: 5238–5248
Mathews MB, Shenk T (1991) Adenovirus virus-associated RNA and translation control. J Virol 65: 5657–5662
Meredith J, Fazeli B, Schwartz MA (1993) The extracellular matrix as a cell survival factor. Mol Biol Cell 4: 953–961
Moran E (1993) Interaction of adenoviral proteins with pRB and p53. FASEB J 7: 880–885
Morrison DC, Jacobs DM (1976) Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides. Immunochemistry 13: 813–818
Nevins JR (1991) Transcriptional activation by viral regulatory proteins. TIBS 16: 435–439
Nevins JR (1992) E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429
Patel G, Jones NC (1990) Activation in vitro of RNA polymerase II and III directed transcription by baculovirus produced E1A protein. Nucleic Acids Res 18: 2909–2915
Plank C, Oberhauser B, Mechtler K, Koch C, Wagner E (1994) The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. J Biol Chem 269: 12918–12924
Raetz CRH (1990) Biochemistry of endotoxins. Annu Rev Biochem 59: 129–170
Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E (1992) The adenovirus E1A proteins induce apoptosis which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci USA 89: 7742–7746
Ruoslahti R, Reed J (1994) Anchorage dependence, integrins and apoptosis. Cell 77: 477–478
Silver L, Anderson C (1988) Interaction of human adenovirus serotype 2 with human lymphoid cells. Virology 165: 377–387
Spergel J, Chen-Kiang S (1991) IL-6 enhances a cellular activity which functionally substitutes for E1A in transactivation. Proc Natl Acad Sci USA 88: 6472–6476
Spergel J, Hsu W, Akira S, Thimmappaya B, Kishimoto T, Chen-Kiang S (1992) NF-IL6, a member of the C/EBP family, regulates E1A-responsive promoters in the absence of E1A. J Virol 66: 1021–1030
Storm DR, Rosenthal KS, Swanson PE (1977) Polymyxin and related peptide antibiotics. Annu Rev Biochem 46: 723–763
Thurnher M, Wagner E, Clausen H, Mechtler K, Rusconi S, Dinter A, Berger E, Bimstiel M, Cotten M (1994) Carbohydrate receptor-mediated gene transfer to human T-leukemic cells. Glycobiology 4: 429–435
Vallat VP, Gilleaudeau P, Battat L, Wolfe J, Nabeya R, Heftier N, Hodak E, Gottlieb AB, Krueger JG (1994) PUVA bath therapy strongly suppresses immunological and epidermal activation in psoriasis: a possible cellular basis for remittive therapy. J Exp Med 180: 283–296
Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel D, Bimstiel ML (1992a) Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected cells. Proc Natl Acad Sci USA 89: 6099–6103
Wagner E, Plank C, Zatloukal K, Cotten M, Bimstiel ML (1992b) Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci USA 89: 7934–7938
Wagner E, Curiel D, Cotten M (1994) Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis. Adv Drug Deliv Rev 14: 113–135
Weinberg DH, Ketner G (1983) A cell line that supports the growth of a defective early region 4 deletion mutant of human adenovirus type 2. Proc Natl Acad Sci USA 80: 5383–5386
White E, Gooding LR (1994) Regulation of apoptosis by human adenoviruses. (Apoptosis II: the molecular basis of apoptosis in disease.) Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Wickham TJ, Mathias P, Cheresh DA, Nemerow GR (1993) Integrins αvβ3 or αvβ5 promote adenovirus internalization but not virus attachment. Cell 73: 309–319
Wold WSM (1993) Adenovirus genes that modulate the sensitivity of virus-infected cells to lysis by TNF. J Cell Biochem 53: 329–335
Wold WSM, Gooding LR (1991) Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology 184: 1–8
Wu G, Zhan P, Sze L, Rosenberg A, Wu C (1994) Incorporation of adenovirus into a ligand-based DNA carrier system results in retention of original receptor specificity and enhances targeted gene expression. J Biol Chem 269: 11542–11546
Wu X, Levine AJ (1994) p53 and E2F-1 cooperate to mediate apoptosis. Proc Natl Acad Sci USA 91: 3602–3606
Yoshimura K, Rosenfeld M, Seth P, Crystal R (1993) Adenovirus-mediated augmentation of cell transfection with unmodified plasmid vectors. J Biol Chem 268: 2300–2303
Yoshinaga S, Dean N, Han M, Berk AJ (1986) Adenovirus stimulation of transcription by RNA polymerase III: evidence for an E1A-dependent increase in transcription factor IIIC concentration. EM BO J 5: 343–354
Zatloukal K, Wagner E, Cotten M, Phillips S, Plank C, Steinlein P, Curiel D, Bimstiel ML (1992) Transferrinfection: a highly efficient way to express gene constructs in eukaryotic cells. Ann NY Acad Sci 660: 136–153
Zatloukal K, Cotten M, Berger M, Schmidt W, Wagner E, Bimstiel ML (1994) In vivo production of human factor VIII in mice after intrasplenic implantation of primary fibroblasts transfected by receptor-mediated adenovirus-augmented gene delivery. Proc Natl Acad Sci USA 91: 5148–5152
Zhang Y, Schneider RJ (1994) Adenovirus inhibition of cell translation facilitates release of virus particles and enhances degradation of the cytokeratin network. J Virol 68: 2544–2555
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Cotten, M. (1995). Adenovirus-Augmented, Receptor-Mediated Gene Delivery and Some Solutions to the Common Toxicity Problems. In: Doerfler, W., Böhm, P. (eds) The Molecular Repertoire of Adenoviruses III. Current Topics in Microbiology and Immunology, vol 199/3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79586-2_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-79586-2_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-79588-6
Online ISBN: 978-3-642-79586-2
eBook Packages: Springer Book Archive