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In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector,” (1996)

by L Naldini, U Blomer, P Gallay
Venue:Science,
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A third-generation lentivirus vector with a conditional packaging system

by Tom Dull, Romain Zufferey, Michael Kelly, Minh Nguyen, Didier Trono, Luigi Naldini, Updated Information, Tom Dull, Romain Zufferey, Michael Kelly, R. J. Mandel - J , 1998
"... These include: This article cites 46 articles, 29 of which can be accessed free at: ..."
Abstract - Cited by 246 (6 self) - Add to MetaCart
These include: This article cites 46 articles, 29 of which can be accessed free at:
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...lls (8, 15, 16, 25, 26). We previously developed replicationdefective vectors from the lentivirus human immunodeficiency virus (HIV) and showed that they transduce target cells independent of mitosis =-=(32)-=-. The vectors proved highly efficient for in vivo gene delivery and achieved stable long-term expression of the transgene in several target tissues, such as the brain (5, 33), the retina (31), and the...

Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery

by Romain Zufferey, Thomas Dull, Ronald J. M, Dulce Quiroz, Luigi Naldini, Didier Trono, Updated Information, Romain Zufferey, Thomas Dull, Ronald J. Mandel, Anatoly Bukovsky, Dulce Quiroz, Luigi Naldini, Didier Trono - J. Virol , 1998
"... These include: This article cites 31 articles, 21 of which can be accessed free at: ..."
Abstract - Cited by 140 (7 self) - Add to MetaCart
These include: This article cites 31 articles, 21 of which can be accessed free at:
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...rived from human immunodeficiency virus type 1 (HIV-1) allow for the efficient in vivo delivery, integration, and stable expression of transgenes into cells such as neurons, hepatocytes, and myocytes =-=(2, 14, 17, 18)-=-. Although this opens exciting prospects for human gene therapy, the biosafety of HIV-based vectors requires a most careful evaluation, considering the pathogenicity of the parental virus. Two compone...

Development of a self-inactivating lentivirus vector

by Hiroyuki Miyoshi, Masayo Takahashi, Fred H. Gage, Inder, M. Verma - J Virol , 1998
"... We have constructed a new series of lentivirus vectors based on human immunodeficiency virus type 1 (HIV-1) that can transduce nondividing cells. The U3 region of the 5 * long terminal repeat (LTR) in vector constructs was replaced with the cytomegalovirus (CMV) promoter, resulting in Tat-independen ..."
Abstract - Cited by 140 (9 self) - Add to MetaCart
We have constructed a new series of lentivirus vectors based on human immunodeficiency virus type 1 (HIV-1) that can transduce nondividing cells. The U3 region of the 5 * long terminal repeat (LTR) in vector constructs was replaced with the cytomegalovirus (CMV) promoter, resulting in Tat-independent transcription but still maintaining high levels of expression. A self-inactivating (SIN) vector was constructed by deleting 133 bp in the U3 region of the 3 * LTR, including the TATA box and binding sites for transcription factors Sp1 and NF-kB. The deletion is transferred to the 5 * LTR after reverse transcription and integration in infected cells, resulting in the transcriptional inactivation of the LTR in the proviruses. SIN viruses can be generated with no significant decreases in titer. Injection of viruses into the rat brain showed that a SIN vector containing the green fluorescent protein gene under the control of the internal CMV promoter transduced neurons as efficiently as a wild-type vector. Interestingly, a wild-type vector without an internal promoter also successfully transduced neurons in the brain, indicating that the HIV-1 LTR promoter is transcriptionally active in neurons even in the absence of Tat. Furthermore, injection of viruses into the subretinal space of the rat eye showed that wild-type vector transduced predominantly retinal pigment epithelium and photoreceptor cells, while SIN vector was able to transduce other types of retinal cells, including bipolar, Müller, horizontal, and amacrine cells. This finding suggests that the HIV-1 LTR can negatively influence the internal CMV promoter in some
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...immunodeficiency virus type 1 (HIV-1) can infect nondividing cells (7, 30, 49). We have recently developed a lentivirus vector based on HIV-1 that can transduce nondividing cells in vitro and in vivo =-=(38)-=-. These HIV vectors are pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G); hence they can transduce a broad range of tissues and can be concentrated to high titers. We have shown ...

HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101:173–185

by Véronique Zennou, Caroline Petit, Denise Guetard, Ulf Nerhbass, Luc Montagnier, Pierre Charneau, Unité D’oncologie Virale , 2000
"... differentiated primary macrophages (Gartner et al., 1986). HIV DNA integrates in the chromatin of nonmitotic target cells (Weinberg et al., 1991), implying that HIV-1 PICs are able to cross the nuclear membrane of host cells (Bukrinsky et al., 1992). Thus, mitosis-independent nuclear import is a piv ..."
Abstract - Cited by 112 (3 self) - Add to MetaCart
differentiated primary macrophages (Gartner et al., 1986). HIV DNA integrates in the chromatin of nonmitotic target cells (Weinberg et al., 1991), implying that HIV-1 PICs are able to cross the nuclear membrane of host cells (Bukrinsky et al., 1992). Thus, mitosis-independent nuclear import is a pivotal event responsible for the ability of HIV and other lentiviruses to replicate in nondi-
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...l gene transfer vectors of HIV-1 is involved in viral genome nuclear import. Thus, with promising therapeutic applications (Poznansky et the reverse-transcribed HIV-1 genome bears a cis-actal., 1991; =-=Naldini et al., 1996-=-). ing determinant for its nuclear import. We also show The mitosis-independent replication of lentiviruses that HIV-1 gene transfer vectors lacking the central DNA was first demonstrated by the produ...

Characterization of intracellular reverse transcription complexes of Moloney murine leukemia virus

by Ariberto Fassati, Stephen P. Goff, Ariberto Fassati, Stephen, P. Goff - J. Virol , 1999
"... This article cites 32 articles, 16 of which can be accessed free ..."
Abstract - Cited by 102 (8 self) - Add to MetaCart
This article cites 32 articles, 16 of which can be accessed free
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...integrate DNAs into the host cell genome (21). However, a major limitation of MLVbased vectors is their inability to infect nondividing cells (18, 22, 28), as opposed to vectors based on lentiviruses =-=(24)-=-. The reasons for the inability of MLV-based vectors to infect nondividing cells are uncertain; the large size of their PIC or the lack of appropriate nuclear targeting signals may be responsible. A m...

Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector

by X Xiao, J Li, R J Samulski, Xiao Juan Li, Richard Jude Samulski - J , 1996
"... adeno-associated virus vector. tissue of immunocompetent mice by Efficient long-term gene transfer into muscle ..."
Abstract - Cited by 101 (12 self) - Add to MetaCart
adeno-associated virus vector. tissue of immunocompetent mice by Efficient long-term gene transfer into muscle
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...as resulted in the need for further vector modification (39). Recent reports of human immunodeficiency virus-based vectors capable of transducing nondividing cells may provide an alternative strategy =-=(38)-=-. However, the safety and efficiency of these promising vectors remain to be tested (38). Contrary to retroviruses, recombinant adenovirus (rAd)- based vectors are able to infect both dividing and non...

Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference

by Maciej Wiznerowicz, Didier Trono, Lentivirus Vector-mediated Drug-inducible, Maciej Wiznerowicz, Didier Trono - J. Virol , 2003
"... This article cites 20 articles, 12 of which can be accessed free at: ..."
Abstract - Cited by 92 (5 self) - Add to MetaCart
This article cites 20 articles, 12 of which can be accessed free at:

The hepatitis B virus posttranscriptional regulatory element is composed of two subelements

by Romain Zufferey, John E. Donello, Didier Trono, Thomas J. Hope - J , 1996
"... The expression of genes delivered by retroviral vectors is often inefficient, a potential obstacle for their widespread use in human gene therapy. Here, we explored the possibility that the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE) might help resolve this problem. In ..."
Abstract - Cited by 86 (9 self) - Add to MetaCart
The expression of genes delivered by retroviral vectors is often inefficient, a potential obstacle for their widespread use in human gene therapy. Here, we explored the possibility that the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE) might help resolve this problem. Insertion of the WPRE in the 3 � untranslated region of coding sequences carried by either oncoretroviral or lentiviral vectors substantially increased their levels of expression in a transgene-, promoter- and vector-independent manner. The WPRE thus increased either luciferase or green fluorescent protein production five- to eightfold, and effects of a comparable magnitude were observed with either the immediate-early cytomegalovirus or the herpesvirus thymidine kinase promoter and with both human immunodeficiency virus- and murine leukemia virus-based vectors. The WPRE exerted this influence only when placed in the sense orientation, consistent with its predicted posttranscriptional mechanism of action. These results demonstrate that the WPRE significantly improves the performance of retroviral vectors and emphasize that posttranscriptional regulation of gene expression should be taken into account in the design of gene delivery systems. Retroviral vectors offer several characteristics of great value for a gene delivery system, including a large packaging capacity, an efficient integration machinery, and the absence of a
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...dotyped transducing particles, vector plasmids with or without the WPRE were cotransfected into 293T cells with the envelope plasmid pMD.G and the packaging plasmid pCMV�R8.91 by a published protocol =-=(20)-=-. The resulting vectors were used to transduce in parallel different cell lines. These experiments were done at a multiplicity of infection (MOI) of 0.1 to favor a single integration per cell. Dilutio...

Species-specific, postentry barriers to primate immunodeficiency virus infection

by Wolfgang Hofmann, David Schubert, Jason Labonte, Susan Gibson, Jonathan Scammell, Paul Ferrigno, Joseph Sodroski, J. Virol, Wolfgang Hofmann, David Schubert, Jason Labonte, Linda Munson, Susan Gibson, Jonathan Scammell, Paul Ferrigno, Joseph Sodroski - J , 1999
"... These include: This article cites 57 articles, 29 of which can be accessed free at: ..."
Abstract - Cited by 52 (10 self) - Add to MetaCart
These include: This article cites 57 articles, 29 of which can be accessed free at:
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...rimate species by HIV-1, SIV, and MuLV vectors. Because it has been shown that cells from some nonprimate species can be infected by HIV-1 vectors pseudotyped with heterologous envelope glycoproteins =-=(32, 46)-=-, restriction against HIV-1 infection must not exist at FIG. 3. Infectibility of primary cells by HIV-1, SIV mac, and MuLV vectors. Primary cells from rhesus monkeys (A), tree shrews (B), and squirrel...

Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles

by Scott L. Butler - J , 2002
"... Early steps of retroviral replication involve reverse transcription of the viral RNA to yield a linear double-stranded cDNA copy and then integration of the viral cDNA into a chromosome of the host cell. A portion of the viral cDNA can also follow nonproductive pathways in which it becomes circulari ..."
Abstract - Cited by 45 (2 self) - Add to MetaCart
Early steps of retroviral replication involve reverse transcription of the viral RNA to yield a linear double-stranded cDNA copy and then integration of the viral cDNA into a chromosome of the host cell. A portion of the viral cDNA can also follow nonproductive pathways in which it becomes circularized. In one pathway, the ends of the linear cDNA become joined together by the cellular nonhomologous DNA end-joining system to form two-long terminal repeat (2-LTR) circles. It has been argued that 2-LTR circles are quickly degraded in human immunodeficiency virus (HIV)-infected cells, allowing the presence of 2-LTR circles to be used as a marker for ongoing de novo infection in patients. Following this idea, detection of 2-LTR circles in patients undergoing successful highly active antiretroviral therapy has led to the proposal that viral replication persists despite treatment. We have used fluorescence-monitored PCR (Taqman) to quantitate the metabolism of HIV cDNA early after infection. Contrary to previous work, we find that 2-LTR circles are actually quite stable in experiments where confounding variables are controlled. Thus, studies relying on the lability of 2-LTR circles are open to reinterpretation. We also used the quantitative PCR methods to analyze the effects of MG132, a proteasome inhibitor, which revealed that viral complexes containing mostly completed cDNAs are the primary substrates for proteasome-mediated degradation. Following introduction of the viral core into the cell cyto-
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...sing a standard curve made with infected-cell DNA as described elsewhere (2). In some studies we have used HIV-based vectors instead of replication-competent HIV to minimize the toxicity of infection =-=(4, 14, 26)-=-. The system used yields particles containing the HIV Gag and Pol proteins and a vector RNA transducing the gene for green fluorescent protein (gfp), all packaged as pseudotypes with the vesicular sto...

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