Long-term protection of recipient mice from lethal doses of methotrexate by marrow infected with a double-copy vector retrovirus containing a mutant dihydrofolate reductase.

S. C. Zhao, M. X. Li, D. Banerjee, B. I. Schweitzer, S. Mineishi, Eli Gilboa, J. R. Bertino

Research output: Contribution to journalArticle

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Abstract

A double-copy Moloney murine leukemia virus-based retroviral construct containing both the NEOr gene and a mutated dihydrofolate reductase cDNA (Leu 22-->Arg) was used to infect mouse bone marrow cells. The infected mouse marrow was returned to lethally irradiated mice. Primary, secondary, and even tertiary recipients transplanted with bone marrow cells infected with the recombinant virus showed protection from lethal methotrexate toxicity. The viral construct containing a SV-40 promoter in the U3 region of the 3' long terminal repeat appeared to be more effective than a similar construct containing the adenosine deaminase promoter, although both afforded protection. Evidence for integration into blood cells of both the NEOr gene and the mutated dihydrofolate reductase gene was obtained by polymerase chain reaction; sequencing of the amplified dihydrofolate reductase cDNA showed the presence of the point mutation. These results indicate that early hematopoietic progenitor cells in the mouse can be successfully transduced with a drug resistance gene.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalCancer Gene Therapy
Volume1
Issue number1
StatePublished - Mar 1 1994
Externally publishedYes

Fingerprint

Tetrahydrofolate Dehydrogenase
Retroviridae
Methotrexate
Bone Marrow
Bone Marrow Cells
Genes
Complementary DNA
Moloney murine leukemia virus
Adenosine Deaminase
Terminal Repeat Sequences
Hematopoietic Stem Cells
Point Mutation
Drug Resistance
Blood Cells
Viruses
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Long-term protection of recipient mice from lethal doses of methotrexate by marrow infected with a double-copy vector retrovirus containing a mutant dihydrofolate reductase. / Zhao, S. C.; Li, M. X.; Banerjee, D.; Schweitzer, B. I.; Mineishi, S.; Gilboa, Eli; Bertino, J. R.

In: Cancer Gene Therapy, Vol. 1, No. 1, 01.03.1994, p. 27-33.

Research output: Contribution to journalArticle

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AU - Bertino, J. R.

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