Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1995-06-07
1999-01-12
Rories, Charles C.P.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
800DIG1, 800DIG2, 800DIG3, 536 241, 435 6, 435 691, 435 911, 4351721, 4351723, 4353201, 435325, 435326, 435355, 435372, 435375, C12N 1579, C12N 1563, C12N 1585, C12N 510
Patent
active
058593098
ABSTRACT:
A vector for the integration of a gene into the genetic material of a mammalian host cell such that the gene may be expressed by the host cell. The vector comprises a promoter and the gene and an immunoglobulin dominant control region derived from the mouse .lambda. immunoglobulin gene locus capable of eliciting host cell-type restricted, integration site independent, copy number dependent expression of the said gene. The DNaseI super hypersensitive site exemplified are i) about 2.35 kb upstream of the CAP site of the rearranged .lambda..sub.1 gene, ii) about 2.5 kb upstream of the genomic V.lambda..sub.2 segment or iii) about 30 kb downstream of the rearranged .lambda..sub.1 gene. Mammalian host cells transformed with the vector are disclosed as are transgenic mammals transformed with the vector and a method of producing a polypeptide comprising culturing a transformed mammalian cell. A method of gene therapy comprising the steps of i) removing stem cells from the body of a mammal, ii) optionally killing stem cells remaining in the body, iii) transforming the removed stem cells with the containing a gene deficient or absent in the body, and iv) replacing the transformed stem cells in the body is also disclosed. Also disclosed is functional mouse immunoglobulin .lambda..sub.1 enhancer consisting of a DNA sequence comprising all or a functional part of the DNA sequence between the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse .lambda..sub.1 gene and the SnaBI site 10 kb downstream of this Xho I site. The functional mouse immunoglobulin .lambda..sub.1 enhancer may comprise all or a functional part of i) the 1.3 kb first HindIII to HindII DNA fragment downstream of the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse .lambda..sub.1 gene, ii) the 3.3 kb HindII to HindII DNA fragment downstream of the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse .lambda..sub.1 gene and spanning the SnaBI site 10 kb downstream of this Xho I site.
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Eccles Sarah Jane
Grosveld Franklin Gerardus
Medical Research Council Ltd.
Rories Charles C.P.
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