A History of Gene Transfer and Therapy

Wolff, Jon A.; Lederberg, Joshua

doi:10.1007/978-1-4684-6822-9_1

Cited by 10 publications

(6 citation statements)

References 138 publications

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“…48 All quantitative assays were performed at least in triplicate and confidence intervals representing mycin, supplemented with 10% fetal bovine serum. Cells were grown in a humidified 37°C incubator with 5% CO 2 the standard error of the mean are shown. as adherent cultures on plastic dishes and passaged at confluence by trypsin-EDTA treatment.…”

Section: Methodsmentioning

confidence: 99%

“…We visually track the course of transfected duce an intact virus from infection of cells with pure viral DNA and observe that all cells are surprisingly com-DNA. 1,2 Several transfection methods have since been petent in the nuclear uptake of foreign DNA, but there developed, including CaPO 4 precipitation, electroporare two liabilities for DNA destruction that limit efficient ation and lipofection. [3][4][5] DNA must first cross the cell transfection to just a minority of cells: obligate routing membrane.…”

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confidence: 99%

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On the mechanism of DNA transfection: efficient gene transfer without viruses

1997

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From an investigation of how transfected DNA navigates abrogation of endosome-lysosome fusion or translocation from the cell surface to the nucleus, we have developed with microfilament or microtubule toxins, respectively, a transfection method for primary human fibroblasts that inhibits the nuclear accumulation of transfected DNA, but approaches the efficiency of viruses. We have visually interruption of lysosomal function with protease inhibitors tracked the subcellular routing of exogenous DNA and find promotes it. Second, in normal human fibroblasts, which that all cells in an asynchronous population are surprisingly are refractory to transfection, the exogenous DNA is rapidly competent in the nuclear uptake of DNA, but two steps excluded from the nucleus, but in HeLa cells, which are practically limit efficient transfection to a minority of cells.readily transfected, there is prolonged nuclear stability of First, regardless of the method used to traverse the cell the DNA, indicating the failure in HeLa cells of a mechanism membrane -CaPO 4 precipitation, lipofection or electroporfor the elimination of foreign DNA. These observations ation -it appears that nuclear transport of DNA requires imply strategies for optimizing gene transfer efficiency in routing through endosomes and lysosomes. Apparent virus-independent approaches to gene therapy.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

On the mechanism of DNA transfection: efficient gene transfer without viruses

1997

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“…Gene therapy using genetically engineered cells and viruses has been applied to diverse medical problems over the past 40 years (Wolff & Lederberg, 1994) and to 350 + clinical trials (Wu et al ., 2001). However, gene therapy for pain control is relatively new.…”

Section: Introductionmentioning

confidence: 99%

Controlling pathological pain by adenovirally driven spinal production of the anti‐inflammatory cytokine, interleukin‐10

Milligan

Langer

Sloane

et al. 2005

Eur J of Neuroscience

196

156

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Gene therapy for the control of pain has, to date, targeted neurons. However, recent evidence supports that spinal cord glia are critical to the creation and maintenance of pain facilitation through the release of proinflammatory cytokines. Because of the ability of interleukin-10 (IL-10) to suppress proinflammatory cytokines, we tested whether an adenoviral vector encoding human IL-10 (AD-h-IL10) would block and reverse pain facilitation. Three pain models were examined, all of which are mediated by spinal pro-inflammatory cytokines. Acute intrathecal administration of rat IL-10 protein itself briefly reversed chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia. The transient reversal caused by IL-10 protein paralleled the half-life of human IL-10 protein in the intrathecal space (t(1/2) approximately 2 h). IL-10 gene therapy both prevented and reversed thermal hyperalgesia and mechanical allodynia, without affecting basal responses to thermal or mechanical stimuli. Extra-territorial, as well as territorial, pain changes were reversed by this treatment. Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far less human IL-10 observed in cervical CSF. In keeping with IL-10's known anti-inflammatory actions, AD-h-IL10 lowered CSF levels of IL-1, relative to control AD. These studies support that this gene therapy approach provides an alternative to neuronally focused drug and gene therapies for clinical pain control.

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“…The first recombinant DNA molecules were constructed in the early 1970s, and genetic manipulation of eukaryotic cells was attempted by the end of the decade. In the 1980s, introduction of exogenous genes into mammalian organs was initiated, and this technology has been extensively used for cell lineage analyses, investigation of gene function and therapeutic approaches to various experimental and human disorders [1,2]. In the kidney, the first trial of renal gene transfer was reported in 1991 [3], and several strategies have been developed during the past 5 years [4 ± 7], as illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

Genetic manipulation of the kidney

Kitamura

Fine

1997

Pediatr Nephrol

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Successful gene transfer into specific renal structures allows for evaluation of in vivo effects of certain molecules on the structure and function of the kidney. It would also be useful for therapeutic intervention in renal diseases by introducing "beneficial" genes into the affected sites. Towards achieving these goals, several gene transfer approaches have been developed using retrovirus, adenovirus and liposome. By introducing these gene transfer vectors via particular access routes, it is feasible to selectively manipulate the function of certain renal structures. Through the renal circulation, exogenous genes can be targeted to the vasculature and glomerulus, and possibly to the proximal tubules. Using a retrograde approach via the urinary tract, access to the collecting ducts can be gained. Implantation of genetically modified cells under the capsule of the kidney allows for diffusion of transgene products into the interstitium. Transplantation of embryonic metanephric tissues also provides a biological window for genetic manipulation. Furthermore, utilisation of fertilised eggs or embryonic stem cells would enable the creation of "transgenic kidneys" or "gene knockout kidneys". This article summarises the current experience with gene transfer to the kidney and addresses the potential strategies in vivo.

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A History of Gene Transfer and Therapy

Cited by 10 publications

References 138 publications

On the mechanism of DNA transfection: efficient gene transfer without viruses

On the mechanism of DNA transfection: efficient gene transfer without viruses

Controlling pathological pain by adenovirally driven spinal production of the anti‐inflammatory cytokine, interleukin‐10

Genetic manipulation of the kidney

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