Home LiteratureArticle Details
PMID: 3459189 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Retroviral transfer of genes into canine hemopoietic progenitor cells in culture: a model for human gene therapy.

Kwok WW, Schuening F, Stead RB, Miller AD

Abstract

Amphotropic retroviral vectors containing either a mutant dihydrofolate reductase gene (DHFR) or the bacterial neomycin phosphotransferase gene (neo) were used to infect canine hemopoietic cells. We report successful transfer and expression of the DHFR and neo genes in canine hemopoietic progenitor cells (colony-forming units, granulocyte/macrophage) as measured by the ability of the viruses to confer resistance to either methotrexate or the aminoglycoside G418, respectively. Transfer was achieved in the absence of helper virus by using retrovirus packaging cell lines. Successful transfer of these genes into canine hemopoietic progenitor cells in vitro indicates the feasibility of gene transfer into canine marrow for autologous reconstitution. Studies of transfer of new genetic information into a large, outbred animal such as the dog will provide a preclinical model for future gene therapy in humans.

MeSH Terms
Animals Bone Marrow Cells Cells, Cultured Dogs Genetic Engineering Genetic Vectors Granulocytes Hematopoietic Stem Cells/physiology Macrophages Retroviridae/genetics Tetrahydrofolate Dehydrogenase/genetics Time Factors
Chemicals
Tetrahydrofolate Dehydrogenase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kwok W W
Schuening F
Stead R B
Miller A D
References (22)
22 references, click to expand
  1. Methotrexate regimens for control of graft-versus-host disease in dogs with allogeneic marrow grafts.
    Transplantation. 1970 Mar;9(3):240-6 PMID: 4392379
  2. Marrow grafts by combined marrow and leukocyte infusions in unrelated dogs selected by histocompatibility typing.
    Transplantation. 1968 Jul;6(4):587-93 PMID: 4876499
  3. Source, alterations, characteristics and use of a new dog cell line (Cf2Th).
    In Vitro. 1976 Oct;12(10):665-9 PMID: 190163
  4. Dimethyl myleran and autologous marrow grafting for the treatment of spontaneous canine lymphoma.
    Eur J Cancer. 1977 Dec;13(12):1411-5 PMID: 340235
  5. Gene transfer in intact animals.
    Nature. 1980 Apr 3;284(5755):422-5 PMID: 6987538
  6. Construction and isolation of a transmissible retrovirus containing the src gene of Harvey murine sarcoma virus and the thymidine kinase gene of herpes simplex virus type 1.
    J Virol. 1981 Sep;39(3):935-44 PMID: 6270359
  7. A new dominant hybrid selective marker for higher eukaryotic cells.
    J Mol Biol. 1981 Jul 25;150(1):1-14 PMID: 6271971
  8. Isolation and expression of an altered mouse dihydrofolate reductase cDNA.
    Proc Natl Acad Sci U S A. 1983 May;80(9):2495-9 PMID: 6573667
  9. Genetic transformation of murine bone marrow cells to methotrexate resistance.
    Blood. 1983 Jul;62(1):180-5 PMID: 6574796
  10. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT.
    Proc Natl Acad Sci U S A. 1983 Aug;80(15):4709-13 PMID: 6308645
  11. Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells.
    Nature. 1983 Oct 6-12;305(5934):556-8 PMID: 6312324
  12. Partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferase-deficient) lymphoblasts with a transmissible retroviral vector.
    J Biol Chem. 1984 Jun 25;259(12):7842-9 PMID: 6203897
  13. Expression of a retrovirus encoding human HPRT in mice.
    Science. 1984 Aug 10;225(4662):630-2 PMID: 6377498
  14. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse.
    Nature. 1984 Aug 9-15;310(5977):476-80 PMID: 6087158
  15. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus.
    Cell. 1983 May;33(1):153-9 PMID: 6678608
  16. Prospects for human gene therapy.
    Science. 1984 Oct 26;226(4673):401-9 PMID: 6093246
  17. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene.
    Mol Cell Biol. 1985 Mar;5(3):431-7 PMID: 2985952
  18. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice.
    Cell. 1985 Aug;42(1):71-9 PMID: 4016956
  19. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors.
    Nature. 1985 Nov 14-20;318(6042):149-54 PMID: 3903518
  20. Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells.
    Nature. 1986 Mar 20-26;320(6059):275-7 PMID: 3960109
  21. Factors involved in production of helper virus-free retrovirus vectors.
    Somat Cell Mol Genet. 1986 Mar;12(2):175-83 PMID: 3457477
  22. Amphotropic host range of naturally occuring wild mouse leukemia viruses.
    J Virol. 1976 Jul;19(1):13-8 PMID: 181592
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1986-06-00
Pages
4552-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323772
Subset
IM
Grants
NCI NIH HHS · CA30924 · United States
NCI NIH HHS · CA31787 · United States
NCI NIH HHS · CA41455 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]