Viruses as gene delivery vectors: application to gene function, target validation, and assay development


Viruses as gene delivery vectors: application to gene function, target validation, and assay development

Play all audios:


ABSTRACT A Biochemical Pharmacology Discussion Group Conference, was held at the headquarters of the New York Academy of Sciences on December 4, 2001 as part of an ongoing series designed to


highlight and review areas important to modern drug development (Figure 1). Briefly introduced by Tom Kost (GlaxoSmithKline) and Michael Lotze (University of Pittsburgh), the focus was on


the intersection of genomics, proteomics, and now “viromics.” The latter term refers to the use of viruses and viral gene transfer to explore the complexity arising from the vast array of


new targets available from the human and murine genomes. Indeed, access to large numbers of genes using viral vectors is a key tool for drug discovery and drug delivery. With 38,000 genes


identified within the human genome, only 5000 are considered readily druggable. Generating tools such as these to validate targets represents a major part of the armamentarium of the


postgenomic scientist. During the last 12 years alone, there have been over 26,000 publications on virus vectors. Many of them have been found useful in target validation, assay development,


and evaluation in _in vivo_ models and gene therapy. Thus, there is now an extensive knowledge base for several viral vectors, with unique attributes within each of them providing


versatility, efficiency, and ease of use. The individual scientists presenting at the meeting illustrated many of the unique and useful characteristics of such vector systems including


retrovirus, adenovirus, herpes virus, simbis virus, and baculovirus. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution


ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article *


Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn


about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS VIRAL VECTOR PLATFORMS WITHIN THE GENE THERAPY LANDSCAPE Article Open


access 08 February 2021 HIGH-THROUGHPUT 5′ UTR ENGINEERING FOR ENHANCED PROTEIN PRODUCTION IN NON-VIRAL GENE THERAPIES Article Open access 06 July 2021 UNCONVENTIONAL VIRAL GENE EXPRESSION


MECHANISMS AS THERAPEUTIC TARGETS Article 19 May 2021 REFERENCES * Grignani F, Kinsella T, Mencarelli A et al. High-efficiency gene transfer and selection of human hematopoietic progenitor


cells with a hybrid EBV/retroviral vector expressing the green fluorescence protein _Cancer Res_ 1998 58: 14–19 CAS  Google Scholar  * Lorens JB, Bennett MK, Pearsall DM et al. Retroviral


delivery of peptide modulators of cellular functions _Mol Ther_ 2000 1: 5 Pt 1 438–447 Article  CAS  PubMed  Google Scholar  * Xu X, Leo C, Jang Y et al. Dominant effector genetics in


mammalian cells _Nat Genet_ 2001 27: 23–29 Article  CAS  PubMed  Google Scholar  * Gilboa E, Goff S, Shields A, Yoshimura F, Mitra S, Baltimore D . _In vitro_ synthesis of a 9 kbp terminally


redundant DNA carrying the infectivity of Moloney murine leukemia virus _Cell_ 1979 16: 863–874 Article  CAS  PubMed  Google Scholar  * Kinoshita S, Chen BK, Kaneshima H, Nolan GP . Host


control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells _Cell_ 1998 95: 595–604 Article  CAS  PubMed  Google Scholar  * Hofmann C, Sandig V, Jennings G, Rudolph M,


Schlag P, Strauss M . Efficient gene transfer into human hepatocytes by baculovirus vectors _Proc Natl Acad Sci USA_ 1995 92: 10099–10103 Article  CAS  PubMed  Google Scholar  * Boyce FM,


Bucher NL . Baculovirus-mediated gene transfer into mammalian cells _Proc Natl Acad Sci USA_ 1996 93: 2348–2352 Article  CAS  PubMed  Google Scholar  * Kost TA, Condreay JP . Recombinant


baculoviruses as mammalian cell gene-delivery vectors _Trends Biotechnol_ 2002 20: 173–180 Article  CAS  PubMed  Google Scholar  * Condreay JP, Witherspoon SM, Clay WC, Kost TA . Transient


and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector _Proc Natl Acad Sci USA_ 1999 96: 127–132 Article  CAS  PubMed  Google Scholar  * Pieroni L,


Maione D, La Monica N . _In vivo_ gene transfer in mouse skeletal muscle mediated by baculovirus vectors _Hum Gene Ther_ 2001 12: 871–881 Article  CAS  PubMed  Google Scholar  * Samaniego


LA, Wu N, DeLuca NA . The herpes simplex virus immediate-early protein ICP0 affects transcription from the viral genome and infected-cell survival in the absence of ICP4 and ICP27 _J Virol_


1997 71: 4614–4625 CAS  PubMed  PubMed Central  Google Scholar  * Fink DJ, DeLuca NA, Yamada M, Wolfe DP, Glorioso JC . Design and application of HSV vectors for neuroprotection _Gene Ther_


2000 7: 115–119 Article  CAS  PubMed  Google Scholar  * Glorioso JC, Fink DJ . Use of HSV vectors to modify the nervous system _Curr Opin Drug Discovery Dev_ 2002 5: 289–295 CAS  Google


Scholar  * Koller D, Ruedl C, Loetscher M et al. A high-throughput alphavirus-based expression cloning system for mammalian cells _Nat Biotechnol_ 2001 19: 851–855 Article  CAS  PubMed 


Google Scholar  * Harvey BG, Leopold PL, Hackett NR et al. Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus _J


Clin Invest_ 1999 104: 1245–1255 Article  CAS  PubMed  PubMed Central  Google Scholar  * Yotnda P, Chen DH, Chiu W et al. Bilamellar cationic liposomes protect adenovectors from preexisting


humoral immune responses _Mol Ther_ 2002 5: 233–241 Article  CAS  PubMed  Google Scholar  * Rosengart TK, Lee LY, Patel SR et al. Six-month assessment of a phase I trial of angiogenic gene


therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA _Ann Surg_ 1999 230: 466–470 discussion


470–472 Article  CAS  PubMed  PubMed Central  Google Scholar  * Kianmanesh A, Hackett NR, Lee JM, Kikuchi T, Korst RJ, Crystal RG . Intratumoral administration of low doses of an adenovirus


vector encoding tumor necrosis factor alpha together with naive dendritic cells elicits significant suppression of tumor growth without toxicity _Hum Gene Ther_ 2001 12: 2035–2049 Article 


CAS  Google Scholar  * Shimizu T, Berhanu A, Redlinger RE Jr, Watkins S, Lotze MT, Barksdale EM Jr . Interleukin-12 transduced dendritic cells induce regression of established murine


neuroblastoma _J Pediatr Surg_ 2001 36: 1285–1292 Article  CAS  PubMed  Google Scholar  * Tanaka F, Hashimoto W, Okamura H, Robbins PD, Lotze MT, Tahara H . Rapid generation of potent and


tumor-specific cytotoxic T lymphocytes by interleukin 18 using dendritic cells and natural killer cells _Cancer Res_ 2000 60: 4838–4844 CAS  Google Scholar  * Lotze MT, Thomson AW . In the


medium is the message: cytokines and dendrikines regulate immune reactivity _Nat Rev Immunol_ In press Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Molecular Genetics


and Biochemistry, University of Pittsburgh Cancer Institute, UPMC Health System, Pittsburgh, 15261, Pennsylvania, USA Michael T Lotze * Gene Expression and Protein Biochemistry,


GlaxoSmithKline Discovery Research, Research Triangle Park, 27709, North Carolina, USA Thomas A Kost Authors * Michael T Lotze View author publications You can also search for this author


inPubMed Google Scholar * Thomas A Kost View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Michael T Lotze. RIGHTS


AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lotze, M., Kost, T. Viruses as gene delivery vectors: Application to gene function, target validation, and assay


development. _Cancer Gene Ther_ 9, 692–699 (2002). https://doi.org/10.1038/sj.cgt.7700493 Download citation * Received: 16 May 2002 * Published: 24 July 2002 * Issue Date: 01 August 2002 *


DOI: https://doi.org/10.1038/sj.cgt.7700493 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not


currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * gene therapy * vectors * gene delivery * target


validation * assay development * retrovirus * adenovirus * herpes virus * simbis virus * baculovirus