Transfer of Genes to Humans: Early Lessons and Obstacles to Success

Crystal, Ronald G.

doi:10.1126/science.270.5235.404

Cited by 984 publications

(523 citation statements)

References 38 publications

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“…Furthermore, cationic liposomes have been shown to be an effective and efficient method for delivery of genetic material to human tissue in vivo. 23,24 Similar gene transfection techniques in human endometrium designed to manipulate HOXA10 expression may allow improved control of human implantation and reproduction. Manipulation of human expression patterns of HOXA10 in the adult endometrium may have potential as a contraceptive or fertility treatment.…”

Section: Discussionmentioning

confidence: 99%

Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

2000

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Mice with a targeted mutation of the Hoxa10 gene demonstrate uterine factor infertility. It is unclear if the defect in the uterine environment arises due to the absence of Hoxa10 expression during embryonic development or in the adult. We have recently demonstrated that HOXA10 expression in human endometrium rises dramatically at the time of implantation, suggesting maternal expression of Hoxa10/HOXA10 may be essential to the process. To assess the importance of maternal Hoxa10 expression, the uteri of day 2 pregnant mice were injected with a DNA/liposome complex containing constructs designed to alter maternal Hoxa10 expression before implantation. Transfection with a Hoxa10 antisense oligodeoxyribonucleotide significantly decreased the number

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Section: Discussionmentioning

confidence: 99%

Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

2000

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“…The delivery of therapeutic gene(s) into target cells using retroviral vectors has been achieusing hollow-fiber filtration technology; 11 and (3) screening of retroviral packaging cell lines using high selection ved in cultured cells and more recently ex vivo in clinical settings. 1 The efficiency with which genes can be intropressure. 12 These methods rely on the original amount of retroviral particles produced, however.…”

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confidence: 99%

Enhancement of retroviral production from packaging cell lines expressing the human immunodeficiency type 1 VPU gene

et al. 1997

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The HIV-1 Vpu protein stimulates virus production by the Damp-VpuP cell line caused a 40-fold increase in the enhancing the release of viral particles from infected cells.titer of infectious virus-like particles when compared with Interestingly, Vpu was also shown to enhance the release control cell lines. This increase in viral titer was not the of capsids produced by gag gene contructs of other retroresult of a clonal effect nor was it a consequence of high viruses that lack a Vpu-like activity. To investigate the selective pressure but rather the effect of a Vpu-mediated effect of Vpu expression on viral particle production in enhancement of viral particle production. Similar results retroviral packaging cell line, we developed the Dampusing the third generation ⌿CRIP packaging cell line conVpuP cell line in which vpu expression is under the control firmed these findings. Constitutive expression of vpu of the tetracycline-responsive promoter. Retroviral procaused a 13-fold increase in viral titer in this packaging cell duction was measured by dosage of virion-associated line. These results indicate that the expression of HIV-1 reverse transcriptase activity, by capsid protein immunovpu in retroviral packaging cell lines can significantly detection in cell-free supernatants and by evaluating the improve the titers of infectious retroviral particles. transfer of antibiotic resistance to target cells. Induction of

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“…Pre-existing immunity against adenovirus would theoretically significantly reduce the uptake of the vector. In addition, the cellular immune response, mediated through adenoviral specific CD8 positive T cells, eliminate the cells' expressing viral and transgene products (24). Overall the undesirable acute immune response to viral proteins was considered the main drawback of virus-based gene therapy (13,14,16).…”

Section: Gene Deliverymentioning

confidence: 99%