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Biomedical subjects

Z Zhang

Publications and source records attributed to Z Zhang.

At least 289 records · Page 16Linked to original sources
PubMed2001

A family of selfish minicircular chromosomes with jumbled chloroplast gene fragments from a dinoflagellate.

Chloroplast genes of several dinoflagellate species are located on unigenic DNA minicircular chromosomes. We have now completely sequenced five aberrant minicircular chromosomes from the dinoflagellate Heterocapsa triquetra. These probably nonfunctional DNA circles lack complete genes, with each being composed of several short fragments of two or three different chloroplast genes and a common conserved region with a tripartite 9G-9A-9G core like the putative replicon origin of functional single-gene circular chloroplast chromosomes. Their sequences imply that all five circles evolved by differential deletions and duplications from common ancestral circles bearing fragments of four genes: psbA, psbC, 16S rRNA, and 23S rRNA. It appears that recombination between separate unigenic chromosomes initially gave intermediate heterodimers, which were subsequently stabilized by deletions that included part or all of one putative replicon origin. We suggest that homologous recombination at the 9G-9A-9G core regions produced a psbA/psbC heterodimer which generated two distinct chimeric circles by differential deletions and duplications. A 23S/16S rRNA heterodimer more likely formed by illegitimate recombination between 16S and 23S rRNA genes. Homologous recombination between the 9G-9A-9G core regions of both heterodimers and additional differential deletions and duplications could then have yielded the other three circles. Near identity of the gene fragments and 9G-9A-9G cores, despite diverging adjacent regions, may be maintained by gene conversion. The conserved organization of the 9G-9A-9G cores alone favors the idea that they are replicon origins and suggests that they may enable the aberrant minicircles to parasitize the chloroplast's replication machinery as selfish circles.

Amino Acid Sequence↗
PubMed2001

Development of a multipurpose feed enzyme analyzer to estimate and evaluate the profitability of using feed enzyme preparations for poultry.

Previous studies have demonstrated that a log-linear equation could accurately predict chick performance when a feed enzyme was added to a diet and that the slope of the equation provided a measure of the efficacy of different enzymes. The objective of the study was to develop a software package, a Multipurpose Feed Enzyme Analyzer (MPFEA), based on an equation designed to evaluate the profitability of using feed enzymes. A high correlation between the efficacy of different feed enzymes (B values, the slopes of the equations) and the maximal profits was obtained when feed enzymes were added to a barley-based diet (r2 = 0.99, P < 0.0005). In contrast, there was a low correlation between the B values and the maximal profits when a feed enzyme was added to different cereal-based diets (r2 = 0.61, P = 0.2171). It appeared that there is not always a close association between efficacy of an enzyme when added to different cereal-based diets and the corresponding profitability. The MPFEA was highly versatile, as any combination of inputs such as the amounts of a feed enzyme and a substituted cereal required to yield a profit level could be determined. In conclusion, the MPFEA can accurately evaluate profitability of using different feed enzymes; select the most profitable cereal for a given feed enzyme; determine the optimal amounts of a feed enzyme, a cereal, or both; and even estimate the alternate price for a feed enzyme and a cereal. It should provide a useful tool for nutritionists.

Animal Feed↗
PubMed2001

Reduction of cardiac norepinephrine improves postischemic heart function in stroke-prone spontaneously hypertensive rats.

Although mammalian ventricle is richly supplied with adrenergic nerves, endogenous norepinephrine is not essential to the intrinsic contractility of the normal heart. However, it is not clear whether acute changes in cardiac norepinephrine could alter heart function in genetically hypertensive rats. The purpose of this study was to examine the effect of cardiac norepinephrine reduction on basal and postischemic heart function in stroke-prone spontaneously hypertensive rats (SHRSPs) using an isolated working heart preparation. Hypertrophied hearts of SHRSPs showed higher cardiac norepinephrine content and impaired heart function at 4 months of age as compared with normal Wistar-Kyoto rats. Poor postischemic recovery of heart function observed in SHRSPs was accompanied by large amounts of coronary norepinephrine overflow. Cardiac norepinephrine reduction or depletion did not affect basal heart function in SHRSPs. Considerable reduction in cardiac norepinephrine with acute reserpine injection (5 mg/kg) in SHRSPs significantly improved postischemic recovery of cardiac output, coronary flow, and rate-pressure product. However, complete norepinephrine depletion with reserpine (10 mg/kg) was detrimental to myocardial automaticity and limited the postischemic recovery of systolic function in the hypertrophied hearts. These results suggest that acute reduction in cardiac norepinephrine may be of potential therapeutic importance to postischemic dysfunction in the hypertrophied hearts.

Animals↗
PubMed2001

Clarification of the relationship between the members of the family Thermomonosporaceae on the basis of 16S rDNA, 16S-23S rRNA internal transcribed spacer and 23S rDNA sequences and chemotaxonomic analyses.

To resolve relationships between members of the family Thermomonosporaceae, phylogenetic analyses using three sets of nucleotide sequences from 16S rDNA, 23S rDNA and the 16S-23S internal transcribed spacer (ITS) were carried out. Nearly all species of the family were included in this study. On the basis of congruous phylogenetic results and chemotaxonomic data, the following proposals are made. First, Actinomadura libanotica, Actinomadura aurantiaca, Actinomadura glomerata and Actinomadura longicatena are transferred to the genus Actinocorallia as Actinocorallia libanotica comb. nov., Actinocorallia aurantiaca comb. nov., Actinocorallia glomerata comb. nov. and Actinocorallia longicatena comb. nov., respectively. All the species of this genus are phylogenetically coherent and of phospholipid type PII (presence of phosphatidylethanolamine), distinguishing them from other Actinomadura species that are of phospholipid type PI (absence of diagnostic phospholipids). Second, Excellospora viridilutea is transferred to the genus Actinomadura as Actinomadura viridilutea comb. nov. As a result of the proposed transfers, the family Thermomonosporaceae now contains four genera Thermomonospora, Actinomadura, Actinocorallia and Spirillospora. The genus Actinocorallia and family Thermomonosporaceae are redescribed.

Actinomycetales↗
PubMed2001

A novel UDP-glucose transferase is part of the callose synthase complex and interacts with phragmoplastin at the forming cell plate.

Using phragmoplastin as a bait, we isolated an Arabidopsis cDNA encoding a novel UDP-glucose transferase (UGT1). This interaction was confirmed by an in vitro protein--protein interaction assay using purified UGT1 and radiolabeled phragmoplastin. Protein gel blot results revealed that UGT1 is associated with the membrane fraction and copurified with the product-entrapped callose synthase complex. These data suggest that UGT1 may act as a subunit of callose synthase that uses UDP-glucose to synthesize callose, a 1,3-beta-glucan. UGT1 also interacted with Rop1, a Rho-like protein, and this interaction occurred only in its GTP-bound configuration, suggesting that the plant callose synthase may be regulated by Rop1 through the interaction with UGT1. The green fluorescent protein--UGT1 fusion protein was located on the forming cell plate during cytokinesis. We propose that UGT1 may transfer UDP-glucose from sucrose synthase to the callose synthase and thus help form a substrate channel for the synthesis of callose at the forming cell plate.

Arabidopsis↗
PubMed2001

Exploration of the GM1 receptor-binding site of heat-labile enterotoxin and cholera toxin by phenyl-ring-containing galactose derivatives.

Cholera toxin (CT) and the closely related heat-labile enterotoxin of Escherichia coli (LT) are responsible for numerous cases of diarrhea worldwide, leading to considerable morbidity and mortality. The B subunits of these heterohexameric AB(5) toxins form a pentameric arrangement which is responsible for binding to the receptor GM1 of the target epithelial cells of the host. Blocking these B pentamer-receptor interactions forms an avenue for therapeutic intervention. Here, the structural characterization of potential receptor-blocking compounds are described based on the previously identified inhibitor m-nitrophenyl-alpha-D-galactoside (MNPG). The structure of a CTB-MNPG complex confirms that the binding mode of this inhibitor is identical in the two homologous toxins CT and LT and is characterized by a glycosyl linkage geometry that leads to displacement of a well ordered water molecule near the amide group of Gly33 by the O1-substituent of MNPG. This glycosyl geometry is not maintained in the absence of a substituent that can displace this water, as shown by a complex of LTB with p-aminophenyl-alpha-D-galactoside (PAPG). New compounds were synthesized to investigate the feasibility of maintaining the favorable binding interactions exhibited by MNPG while gaining increased affinity through the addition of hydrophobic substituents complementary to either of two hydrophobic regions of the receptor-binding site. The structural characterization of complexes of LTB with two of these compounds, 3-benzylaminocarbonylphenyl-alpha-D-galactoside (BAPG) and 2-phenethyl-7-(2,3-dihydrophthalazine-1,4-dione)-alpha-D-galactoside (PEPG), demonstrates a partial success in this goal. Both compounds exhibit a mixture of binding modes, some of which are presumably influenced by the local packing environment at multiple crystallographically independent binding sites. The terminal phenyl ring of BAPG associates either with the phenyl group of Tyr12 or with the hydrophobic patch formed by Lys34 and Ile58. The latter interaction is also made by the terminal phenyl substituent of PEPG, despite a larger ring system linking the galactose moiety to the terminal phenyl. However, neither BAPG nor PEPG displaces the intended target water molecule. Both of the designed compounds exhibit increased affinity relative to the galactose and to PAPG notwithstanding the failure to displace a bound water, confirming that additional favorable hydrophobic interactions can be gained by extending the starting inhibitor by a hydrophobic tail. The insight gained from these structures should allow the design of additional candidate inhibitors that retain both the glycosyl geometry and water displacement exhibited by MNPG and the favorable hydrophobic interactions exhibited by BAPG and PEPG.

Bacterial Toxins↗
PubMed2001

Disulfide structure of alfimeprase: a recombinant analog of fibrolase.

The disulfide structure of alfimeprase, a recombinant analog of fibrolase, was experimentally determined by a combination of peptide mapping, Edman degradation, and mass spectrometry. The three disulfide bonds were determined to be Cys-116/196, Cys-156 /180, and Cys-158/163 with the residue number system of alfimeprase.

Amino Acid Sequence↗
PubMed2001

Transcriptional control mechanism of fibrinogen gene expression.

Although fibrinogen genes are expressed constitutively in hepatocytes, their transcription can be greatly increased during inflammatory stress. Extensive studies have focused on the cytokine mediated transcriptional regulation of fibrinogen genes. It is clear that interleukin-6 (IL-6) and its family of cytokines are the major inducers of fibrinogen gene expression. Functional analyses of all three fibrinogen promoters for human and rat all demonstrate that the conserved CTGGGAA motifs within the proximal promoter of each fibrinogen gene are the IL-6 responsive elements. Exploration of the rat gamma fibrinogen gene demonstrated that the IL-6 activated transcription factor, STAT3, binds to the CTGGGAA motif and is required for the IL-6 mediated upregulation of this gene. IL-6 mediated fibrinogen production can be significantly elevated by glucocorticoid treatment. The synergistic effect of glucocorticoids and IL-6 relies on the functional interaction between STAT3 and glucocorticoid receptor. In addition to the upregulation signals for fibrinogen gene expression during inflammatory stress, other signaling also downregulates the expression of fibrinogen genes. For example, the proinflammatory cytokine IL-1 beta exerts inhibitory function on IL-6 mediated fibrinogen gene expression. Given the fact that elevated levels of fibrinogen in blood correlate with increased risk for cardiovascular disease, there is strong motivation to explore the molecular mechanisms that control fibrinogen expression, especially those signals that may downmodulate expression and thus provide novel approaches to controlling fibrinogen levels.

Animals↗
PubMed2001

Neurogenesis and neuroprotection in the adult brain. A putative role for 5-lipoxygenase?

5-Lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are two enzymes that are critical for the synthesis of eicosanoids, the inflammatory metabolites of arachidonic acid. Both 5-LOX and COX-2 are expressed in the brain, including in CNS neurons. The physiologic role of these proteins in neuronal functioning is not clear. In non-neuronal tissues these two enzymes often assume similar roles: in addition to their function in inflammation, 5-LOX and COX-2 appear to be associated with cell proliferation, that is, with tumor growth. High 5-LOX expression has been noticed in the proliferating brain or pancreatic tumor cells; reduction in tumor cell proliferation and/or destruction of tumor cells was achieved with 5-LOX inhibitors. Proliferation of immature neurons/neuroblasts is an important component of mitotic neurogenesis. We investigated the role of 5-LOX in proliferation using cultures of human neuronal precursor cells, NT2. We found that these cells express 5-LOX mRNA and we used 3H-thymidine incorporation as a measure of cell proliferation; this was reduced by treating the cultures with 5-LOX inhibitor AA-861. We propose that the 5-LOX pathway plays a crucial role in mitotic neurogenesis. Additional studies should explore whether 5-LOX may participate in neurogenesis related pathologies and whether it should be considered a target for procedures aimed at altering neurogenesis for therapeutic purposes.

Animals↗
PubMed2001

A second quorum-sensing system regulates cell surface properties but not phenazine antibiotic production in Pseudomonas aureofaciens.

The root-associated biological control bacterium Pseudomonas aureofaciens 30-84 produces a range of exoproducts, including protease and phenazines. Phenazine antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI quorum-sensing system. Mutants defective in phzR or phzI produce very low levels of phenazines but wild-type levels of exoprotease. In the present study, a second genomic region of strain 30-84 was identified that, when present in trans, increased beta-galactosidase activity in a genomic phzB::lacZ reporter and partially restored phenazine production to a phzR mutant. Sequence analysis identified two adjacent genes, csaR and csaI, that encode members of the LuxR-LuxI family of regulatory proteins. No putative promoter region is present upstream of the csaI start codon and no lux box-like element was found in either the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component regulatory system. In contrast to the multicopy effects of csaR and csaI in trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not exhibit altered phenazine production in vitro or in situ, indicating that the CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both mutants also produced wild-type levels of protease. However, disruption of both csaI and phzI or both csaR and phzR eliminated both phenazine and protease production completely. Thus, the two quorum-sensing systems do not interact for phenazine regulation but do interact for protease regulation. Additionally, the CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR resulted in a smooth mucoid colony phenotype and formation of cell aggregates in broth, suggesting that CsaR is involved in regulating biosynthesis of cell surface components. Strain 30-84I/I2 exhibited mucoid colony and clumping phenotypes similar to those of 30-84R2. Both phenotypes were reversed by complementation with csaR-csaI or by the addition of the CsaI AHL signal. Both quorum-sensing systems play a role in colonization by strain 30-84. Whereas loss of PhzR resulted in a 6.6-fold decrease in colonization by strain 30-84 on wheat roots in natural soil, a phzR csaR double mutant resulted in a 47-fold decrease. These data suggest that gene(s) regulated by the CsaR-CsaI system also plays a role in the rhizosphere competence of P. aureofaciens 30-84.

4-Butyrolactone↗
PubMed2001

Early diagnosis of scrub typhus with a rapid flow assay using recombinant major outer membrane protein antigen (r56) of Orientia tsutsugamushi.

The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the immunodominant antigen in human scrub typhus infections. We developed a rapid immunochromatographic flow assay (RFA) for the detection of immunoglobulin M (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated recombinant 56-kDa protein from the Karp strain as the antigen. The performance of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85 individuals suspected of scrub typhus) which were collected in the Pescadore Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp whole-cell antigen. In 29 cases specific responses were detected by the RFA earlier than by IFA, 44 cases had the same detection time, and 5 cases were detected earlier by IFA than by RFA. For IgG responses, 4 individuals were negative with both methods, 37 cases exhibited earlier detection by RFA than IFA, 42 cases were detected at the same time, and 2 cases were detected earlier by IFA than by RFA. The sensitivities of RFA detection of antibody in sera from confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG results were combined, the sensitivity was 89%. A panel of 78 individual sera collected from patients with no evidence of scrub typhus was used to evaluate the specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and were 78% when the results of IgM and IgG were combined. The RFA test was significantly better than the IFA test for the early detection of antibody to scrub typhus in primary infections, while both tests were equally sensitive with reinfected individuals.

Antibody Specificity↗
PubMed2001

Shigella infection in a SCID mouse-human intestinal xenograft model: role for neutrophils in containing bacterial dissemination in human intestine.

Shigellae infect human intestine and cause intense inflammation and destruction of colonic and rectal mucosa. To model the interactions of shigella with human intestine in vivo, we have studied shigella infection in human intestinal xenografts in severe combined immunodeficient mice (SCID-HU-INT mice). Inoculation of shigella into human intestinal xenografts caused severe inflammation and mucosal damage, which was apparent as soon as 4 h following infection. Shigella infection was associated with human intestinal production of interleukin-1B (IL-1B) and IL-8 and a marked neutrophil influx into the graft. Depletion of neutrophils from SCID-HU-INT mice reduced inflammation in the human intestinal xenograft in response to shigella infection but failed to significantly alter tissue damage. However, the number of intracellular bacteria was more than 20-fold higher in the human intestinal xenografts from neutrophil-depleted SCID-HU-INT mice. Infection of human intestinal xenografts with an attenuated vaccine strain of shigella (CVD1203) induced lower levels of IL-1B and IL-8 than wild-type shigella and caused only moderate damage to the intestinal permeability barrier. Our studies establish the SCID-HU-INT mouse as a viable model for studying the interactions between shigella and human intestine and indicate that neutrophils are important for controlling the invasion of human intestine by shigella.

Animals↗
PubMed2001

Amebic infection in the human colon induces cyclooxygenase-2.

We sought to determine if infection of the colon with Entamoeba histolytica induces the expression of cyclooxygenase-2 and, if it does, to determine the contribution of prostaglandins produced through cyclooxygenase-2 to the host response to amebic infection. Human fetal intestinal xenografts were implanted subcutaneously in mice with severe combined immunodeficiency and allowed to grow; the xenografts were then infected with E. histolytica trophozoites. Infection with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial cells and lamina propria macrophages. Infection with E. histolytica increased prostaglandin E(2) (PGE2) levels 10-fold in the xenografts and resulted in neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL-8) production and a >100-fold increase in epithelial permeability. Treatment of the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2, resulted in (i) decreased PGE(2) levels, (ii) a decrease in neutrophil infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the enhanced epithelial permeability seen with amebic infection. These results indicate that amebic infection in the colon induces the expression of cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins produced through cyclooxygenase-2 participate in the mediation of the neutrophil response to infection and enhance epithelial permeability.

Animals↗
PubMed2001

Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency.

Reactivation of cytomegalovirus (CMV) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. Previous studies have shown that allogeneic stimulation induces reactivation of human CMV (HCMV) in vitro (64). We find that transplantation of vascularized allogeneic kidneys induces murine CMV (MCMV) and HCMV immediate-early (ie) gene expression. This induction is accompanied by increased expression of transcripts encoding inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-2, and gamma interferon, and by activation of NF-kappaB. TNF alone can substitute for allogeneic transplantation in inducing HCMV and MCMV ie gene expression in some tissues. Our studies suggest that reactivation is a multistep process which is initiated by factors that induce ie gene expression, including TNF and NF-kappaB. Allogeneic transplantation combined with immunosuppression may be required to achieve complete reactivation in vivo.

Animals↗
PubMed2001

Sensitivity of human immunodeficiency virus type 1 to fusion inhibitors targeted to the gp41 first heptad repeat involves distinct regions of gp41 and is consistently modulated by gp120 interactions with the coreceptor.

T-20 is a synthetic peptide that corresponds to 36 amino acids within the C-terminal heptad repeat region (HR2) of human immunodeficiency virus type 1 (HIV-1) gp41. T-20 has been shown to potently inhibit viral replication of HIV-1 both in vitro and in vivo and is currently being evaluated in a Phase III clinical trial. T-649 is an inhibitory peptide that also corresponds to 36 amino acids within HR2. This sequence overlaps the T-20 sequence but is shifted 10 residues toward the N terminus of gp41. Both inhibitors are thought to exert their antiviral activity by interfering with the conformational changes that occur within gp41 to promote membrane fusion following gp120 interactions with CD4 and coreceptor molecules. We have shown previously that coreceptor specificity defined by the V3 loop of gp120 modulates sensitivity to T-20 and that a critical region within the N-terminal heptad repeat (HR1) of gp41 is the major determinant of sensitivity (C. A. Derdeyn et al., J. Virol. 74:8358-8367, 2000). This report shows that (i) regions within gp41 distinct from those associated with T-20 sensitivity govern the baseline sensitivity to T-649 and (ii) T-649 sensitivity of chimeric viruses that contain sequences derived from CXCR4- and CCR5-specific envelopes is also modulated by coreceptor specificity. Moreover, the pattern of sensitivity of CCR5-specific chimeras with only minor differences in their V3 loop was consistent for both inhibitors, suggesting that the individual affinity for coreceptor may influence accessibility of these inhibitors to their target sequence. Finally, an analysis of the sensitivity of 55 primary, inhibitor-naive HIV-1 isolates found that higher concentrations of T-20 (P < 0.001) and T-649 (P = 0.016) were required to inhibit CCR5-specific viruses compared to viruses that utilize CXCR4. The results presented here implicate gp120-coreceptor interactions in driving the complex conformational changes that occur in gp41 to promote fusion and entry and suggest that sensitivity to different HR1-directed fusion inhibitors is governed by distinct regions of gp41 but is consistently modulated by coreceptor specificity.

Amino Acid Sequence↗
PubMed2001

Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages.

Macrophages are thought to represent one of the first cell types in the body to be infected during the early stage of human immunodeficiency virus type 1 (HIV-1) transmission and represent a potential viral reservoir in vivo. Thus, an understanding of HIV-1 attachment to these cells is fundamental to the development of novel anti-HIV-1 therapies. Although one of the major targets of HIV-1 in vivo--CD4(+) T lymphocytes--express high CD4 levels, other major targets such as macrophages do not. We asked in this study whether this low CD4 level on macrophages is sufficient to support HIV-1 attachment to these cells or whether cell surface proteins other than CD4 are required for this process. We show that CD4 alone is not sufficient to support the initial adsorption of HIV-1 to macrophages. Importantly, we find that heparan sulfate proteoglycans (HSPGs) serve as the main class of attachment receptors for HIV-1 on macrophages. Most importantly, we demonstrate that a single family of HSPGs, the syndecans, efficiently mediates HIV-1 attachment and represents an abundant class of attachment receptors on macrophages.

HIV Infections↗
PubMed2001

Efficient c-kit receptor-targeted gene transfer to primary human CD34-selected hematopoietic stem cells.

We have previously reported effective gene transfer with a targeted molecular conjugate adenovirus vector through the c-kit receptor in hematopoietic progenitor cell lines. However, a c-kit-targeted recombinant retroviral vector failed to transduce cells, indicating the existence of significant differences for c-kit target gene transfer between these two viruses. Here we demonstrate that conjugation of an adenovirus to a c-kit-retargeted retrovirus vector enables retroviral transduction. This finding suggests the requirement of endosomalysis for successful c-kit-targeted gene transfer. Furthermore, we show efficient gene transfer to, and high transgene expression (66%) in, CD34-selected, c-kit(+) human peripheral blood stem cells using a c-kit-targeted adenovirus vector. These findings may have important implications for future vector development in c-kit-targeted stem cell gene transfer.

Adenoviridae↗