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November 17, 1993, Vol 270, No. 19 >
ARTICLE | November 17, 1993

Progress Toward Human Gene Therapy FREE

Manal A. Morsy, MD, PhD; Kohnosuke Mitani, PhD; Paula Clemens, MD; C. Thomas Caskey, MD
[+] Author Affiliations

Reprint requests to the Institute for Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 (Dr Caskey).


JAMA. 1993;270(19):2338-2345. doi:10.1001/jama.1993.03510190094033
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References

THE TECHNOLOGY of gene transfer has evolved over nearly 50 years since studies of DNA-mediated bacterial transformation reported by Avery et al in 1944.1 These earliest gene transfer experiments explored "the chemical nature of the substance inducing transformation of pneumococcal types."1 More than two decades later, mammalian cells were transformed with SV40 and polyoma papovavirus DNA by calcium phosphate—mediated cellular uptake.2-4 In 1971, the first workshop on gene therapy was held.5 Recombinant DNA technology provided the first approaches for cell transfer of disease-related genes (ie, β-globin [hemoglobinopathies] and hypoxanthine guanine phosphoribosyltransferase [Lesch-Nyhan syndrome]).6-10 The Human Genome Project, with its high rate of heritable disease and cancer gene discoveries, fuels the opportunities for gene transfer therapy.

Replication-defective viral vectors are essential vehicles for gene transfer. Safe viral vectors were developed in the laboratories of Mulligan, Verma, Miller, and Gilboa based on the basic research on the life

REFERENCES

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Avery OT, McLeod CM, McCarty M.  Studies on the chemical nature of the substance inducing transformation of pneumococcal types. J Exp Med . 1944;; 79:137-158.
2 +
Sambrook J, Westphal H, Srivansan PR, Dulbecco R.  The integrated state of viral DNA in SV40-transformed cells. Proc Natl Acad Sci USA . 1968;; 59:1288-1293.
3 +
Graham FL, Van der Eb AJ.  A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology . 1973;;52:456-467.
4 +
Temin HM.  Mechanism of cell transformation by RNA tumor viruses. Ann Rev Med . 1971;;25:609-649.
5 +
Freese E. The Prospects of Gene Therapy . Bethesda, Md: Fogarty International Center, National Institutes of Health; 1972;.
6 +
Maniatis T, Jim GK, Efstradiadis A, Kafatos F.  Amplification and characterization of the beta-globin gene synthesized in vitro. Cell . 1976;;8:163-182.
7 +
Wigler M, Pellicer A, Silverstein S, Axel R.  Transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell . 1978;;14:725-731.
8 +
Green MR, Treisman R, Maniatis T.  Transcriptional activation of the cloned human beta-globin genes by viral immediate-early gene products. Cell . 1982;;35:137-148.
9 +
Mulligan RC, Berg P.  Selection for animal cells that express the Escherichia coli gene for xanthineguanine phosphoribosyltransferase. Proc Natl Acad Sci U S A . 1981;;78:2072-2076.
10 +
Mulligan RC, Berg P.  Factors governing the expression of a bacterial gene in mammalian cells. Mol Cell Biol . 1981;;1:449-459.
11 +
Mann R, Mulligan RC, Baltimore D.  Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell . 1983;; 33:153-159.
12 +
Miller AD, Law MF, Verma I.  Generation of helper-free amphotropic retroviruses that transduce a dominatant acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol . 1985;; 5:431-437.
13 +
Miller AD, Buttimore C.  Redesign of packaging lines to avoid recombination leading to helper virus production. Mol Cell Biol . 1986;;6:2895-2902.
14 +
Doehmer J, Barinaga M, Vale W, Rosenfeld MG, Verma IM, Evans RM.  Introduction of rat growth hormone into mouse fibroblasts via a retroviral DNA vector. Proc Natl Acad Sci U S A . 1982;;79:2268-2272.
15 +
Shimotohno K, Temin HM.  Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus. Cell . 1981;;26:67-77.
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Tabin CJ, Hoffmann JW, Goff SP, Weinberg RA.  Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex thymidine kinase gene. Mol Cell Biol . 1982;;2:426-436.
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Temin HM.  Retroviral vectors for gene transfer: efficient integration into and expression of exogenous DNA in vertebrate cell genomes.  In: Kucherlapati R, ed. Gene Transfer . New York, NY: Plenum Press; 1986;:149-187.
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Wei C, Gibson M, Spear P, Scolnick EM.  Construction and isolation of a transmissible retrovirus containing the src gene from Harvey Murine Sarcoma Virus and the thymidine kinase gene from herpes simplex virus type 1. J Virol . 1981;;39:935-944.
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Markowitz D, Goff S, Bank A.  A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol . 1988;;62:1120-1124.
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Wolff JA, Malone RW, Williams P, et al.  Direct gene transfer into mouse muscle in vivo. Science . 1990;;247:1465-1468.
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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Avery OT, McLeod CM, McCarty M.  Studies on the chemical nature of the substance inducing transformation of pneumococcal types. J Exp Med . 1944;; 79:137-158.
2 +
Sambrook J, Westphal H, Srivansan PR, Dulbecco R.  The integrated state of viral DNA in SV40-transformed cells. Proc Natl Acad Sci USA . 1968;; 59:1288-1293.
3 +
Graham FL, Van der Eb AJ.  A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology . 1973;;52:456-467.
4 +
Temin HM.  Mechanism of cell transformation by RNA tumor viruses. Ann Rev Med . 1971;;25:609-649.
5 +
Freese E. The Prospects of Gene Therapy . Bethesda, Md: Fogarty International Center, National Institutes of Health; 1972;.
6 +
Maniatis T, Jim GK, Efstradiadis A, Kafatos F.  Amplification and characterization of the beta-globin gene synthesized in vitro. Cell . 1976;;8:163-182.
7 +
Wigler M, Pellicer A, Silverstein S, Axel R.  Transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell . 1978;;14:725-731.
8 +
Green MR, Treisman R, Maniatis T.  Transcriptional activation of the cloned human beta-globin genes by viral immediate-early gene products. Cell . 1982;;35:137-148.
9 +
Mulligan RC, Berg P.  Selection for animal cells that express the Escherichia coli gene for xanthineguanine phosphoribosyltransferase. Proc Natl Acad Sci U S A . 1981;;78:2072-2076.
10 +
Mulligan RC, Berg P.  Factors governing the expression of a bacterial gene in mammalian cells. Mol Cell Biol . 1981;;1:449-459.
11 +
Mann R, Mulligan RC, Baltimore D.  Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell . 1983;; 33:153-159.
12 +
Miller AD, Law MF, Verma I.  Generation of helper-free amphotropic retroviruses that transduce a dominatant acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol . 1985;; 5:431-437.
13 +
Miller AD, Buttimore C.  Redesign of packaging lines to avoid recombination leading to helper virus production. Mol Cell Biol . 1986;;6:2895-2902.
14 +
Doehmer J, Barinaga M, Vale W, Rosenfeld MG, Verma IM, Evans RM.  Introduction of rat growth hormone into mouse fibroblasts via a retroviral DNA vector. Proc Natl Acad Sci U S A . 1982;;79:2268-2272.
15 +
Shimotohno K, Temin HM.  Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus. Cell . 1981;;26:67-77.
16 +
Tabin CJ, Hoffmann JW, Goff SP, Weinberg RA.  Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex thymidine kinase gene. Mol Cell Biol . 1982;;2:426-436.
17 +
Temin HM.  Retroviral vectors for gene transfer: efficient integration into and expression of exogenous DNA in vertebrate cell genomes.  In: Kucherlapati R, ed. Gene Transfer . New York, NY: Plenum Press; 1986;:149-187.
18 +
Wei C, Gibson M, Spear P, Scolnick EM.  Construction and isolation of a transmissible retrovirus containing the src gene from Harvey Murine Sarcoma Virus and the thymidine kinase gene from herpes simplex virus type 1. J Virol . 1981;;39:935-944.
19 +
Markowitz D, Goff S, Bank A.  A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol . 1988;;62:1120-1124.
20 +
Wolff JA, Malone RW, Williams P, et al.  Direct gene transfer into mouse muscle in vivo. Science . 1990;;247:1465-1468.
21 +
Yang N-S, Burkholder J, Roberts B, Martinell B, McCabe D.  In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci U S A . 1990;;87:9568-9572.
22 +
Graham FL, Prevec L.  Manipulation of adenovirus vectors.  In: Murray EJ, eds. Methods in Molecular Biology: Gene Transfer and Expression Protocols . Clinton, NJ: The Humana Press Inc; 1991;: 109-128.
23 +
Horwitz MS.  Adenoviruses.  In: Fields BN, Knipe DM, eds. Field's Virology . 2nd ed. New York, NY: Raven Press; 1990;:1679-1721.
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