DNA/Amphiphilic Block Copolymer Nanospheres Promote Low-dose DNA Vaccination

McIlroy, Dorian; Barteau, Benoit; Cany, Jeannette; Richard, Peggy; Gourden, Clothilde; Conchon, Sophie; Pitard, Bruno

doi:10.1038/mt.2009.84

Cited by 33 publications

(38 citation statements)

References 47 publications

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“…Formulations containing 0.25% (w v À1 ) 704 increased the expression of CAT when compared with 904 and 304 ( Figure 1a), which have been previously shown to improve the transfection efficiency in skeletal and cardiac muscles. 21,23,25 We also evaluated the transfection efficiency of PEI and Lutrol, which have been previously shown to improve the transfection efficiency in lungs. 22,26 Figure 1b illustrates that 704/DNA complexes increased CAT expression compared with that obtained with the maximally effective doses of DNA complexed with Lutrol or PEI.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, the tetrafunctional block copolymer 704 has already proven very attractive for its transfection efficiency in skeletal muscles, leading to high transgene expression eliciting strong humoral and cellular responses specific to the expressed antigen by gene transfer. 23 Here, we have evaluated the efficacy of several amphiphilic block copolymers to deliver genes within lung tissues in mice. Among the tetrafunctional block copolymers tested, 704 was the most efficient in lung gene transfer.…”

Section: Discussionmentioning

confidence: 99%

“…Stock solutions were prepared at 20% (w v À1 ) in water and stored at 4 1C. Formulations of DNA with Lutrol or tetrafunctional block copolymers were prepared by equivolumetric mixing of Lutrol or tetrafunctional block copolymers at various concentrations in water with plasmid DNA FKN-Fc/704 aerosolization to tumor lungs P Richard-Fiardo et al solution at the desired concentration as described by McIlroy et al 23 Complexes of poly(ethyleneimine) (25 kDa) PEI/DNA were prepared as described previously 24 in Hepes 10 mM, pH 7.4. Complexes were administrated at a PEI/ DNA charge ratios ( þ /À) of 2.…”

Section: Cell Transfectionmentioning

confidence: 99%

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Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

et al. 2011

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The lung is one target organ to which solid tumors frequently metastasize. Given the systemic adverse effects of currently available treatments, developing effective strategies of drug/gene delivery directly to the lungs is therefore needed. Aerosol delivery is a noninvasive gene transfer approach to target the airways. Here, we sought to evaluate the potential to deliver a fractalkine (FKN)-encoding plasmid formulated with the tetrafunctional amphiphilic block copolymer 704 through aerosolization in two models of pulmonary metastases. FKN is a chemokine recently described as a good candidate to stimulate a strong antitumor immune response in various forms of cancers. Here, we have assessed the effect of single and repeated aerosolizations of FKN-encoding plasmid formulated with 704 on the development of experimental lung metastases of mouse colon carcinoma and osteosarcoma. For this purpose, we have designed FKN-Fc sequences encoding an optimized version of the chemokine. Repeated intratracheal administrations of 704/FKN-Fc markedly inhibited growth of experimental lung metastases of CT-26 and K7M2 cells. Our results showed that tetrafunctional amphiphilic block copolymer 704 is a highly efficient synthetic vector for mediating local and safe gene transfer into the lung. In addition, FKN-Fc gene therapy of pulmonary nodules may provide a promising immunotherapeutic approach.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cell Transfectionmentioning

confidence: 99%

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Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

et al. 2011

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“…34,35 Based on previous studies and the preferred route of DNA vaccine injections, we used the intramuscular route for our studies. 36 In one previous study, a plasmid DNA nanopolymer vaccine showed elevated transgene expression and antigen presentation when injected via the skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

A nonviral pHEMA+chitosan nanosphere-mediated high-efficiency gene delivery system

Eroğlu¹,

Tiwari²,

Waffo³

et al. 2013

IJN

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Abstract:The transport of DNA into eukaryotic cells is minimal because of the cell membrane barrier, and this limits the application of DNA vaccines, gene silencing, and gene therapy. Several available transfection reagents and techniques have been used to circumvent this problem. Alternatively, nonviral nanoscale vectors have been shown to bypass the eukaryotic cell membrane. In the present work, we developed a unique nanomaterial, pHEMA+chitosan nanospheres (PCNSs), which consisted of poly(2-hydroxyethyl methacrylate) nanospheres surrounded by a chitosan cationic shell, and we used this for encapsulation of a respiratory syncytial virus (RSV)-F gene construct (a model for a DNA vaccine). The new nanomaterial was capable of transfecting various eukaryotic cell lines without the use of a commercial transfection reagent. Using transmission electron microscopy, (TEM), fluorescence activated cell sorting (FACS), and immunofluorescence, we clearly demonstrated that the positively charged PCNSs were able to bind to the negatively charged cell membrane and were taken up by endocytosis, in Cos-7 cells. Using quantitative polymerase chain reaction (qPCR), we also evaluated the efficiency of transfection achieved with PCNSs and without the use of a liposomal-based transfection mediator, in Cos-7, HEp-2, and Vero cells. To assess the transfection efficiency of the PCNSs in vivo, these novel nanomaterials containing RSV-F gene were injected intramuscularly into BALB/c mice, resulting in high copy number of the transgene. In this study, we report, for the first time, the application of the PCNSs as a nanovehicle for gene delivery in vitro and in vivo.

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“…S1 in the supplemental material was followed because it was successfully used with other antigens as reported earlier (13). We used a synthetic delivery system composed of a tetrafunctional 704 block copolymer that has been shown to increase dramatically the vaccination efficiency over that seen with naked DNA in mouse model (30). The polymer was administered by intramuscular injection.…”

Section: Methodsmentioning

confidence: 99%

MgtC as a Host-Induced Factor and Vaccine Candidate against Mycobacterium abscessus Infection

et al. 2016

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g Mycobacterium abscessus is an emerging pathogenic mycobacterium involved in pulmonary and mucocutaneous infections, presenting a serious threat for patients with cystic fibrosis (CF). The lack of an efficient treatment regimen and the emergence of multidrug resistance in clinical isolates require the development of new therapeutic strategies against this pathogen. Reverse genetics has revealed genes that are present in M. abscessus but absent from saprophytic mycobacteria and that are potentially involved in pathogenicity. Among them, MAB_3593 encodes MgtC, a known virulence factor involved in intramacrophage survival and adaptation to Mg 2؉ deprivation in several major bacterial pathogens. Here, we demonstrated a strong induction of M. abscessus MgtC at both the transcriptional and translational levels when bacteria reside inside macrophages or upon Mg 2؉ deprivation. Moreover, we showed that M. abscessus MgtC was recognized by sera from M. abscessus-infected CF patients. The intramacrophage growth (J774 or THP1 cells) of a M. abscessus knockout mgtC mutant was, however, not significantly impeded. Importantly, our results indicated that inhibition of MgtC in vivo through immunization with M. abscessus mgtC DNA, formulated with a tetrafunctional amphiphilic block copolymer, exerted a protective effect against an aerosolized M. abscessus challenge in CF (⌬F508 FVB) mice. The formulated DNA immunization was likely associated with the production of specific MgtC antibodies, which may stimulate a protective effect by counteracting MgtC activity during M. abscessus infection. These results emphasize the importance of M. abscessus MgtC in vivo and provide a basis for the development of novel therapeutic tools against pulmonary M. abscessus infections in CF patients. Mycobacterium abscessus, a rapidly growing mycobacterium (RGM), is the etiological agent of a wide spectrum of infections in humans. M. abscessus is responsible for severe and persistent pulmonary infections, disseminated cutaneous diseases, and posttrauma and postsurgery wound infections, mostly in immunocompetent patients and in cystic fibrosis (CF) patients (1-5). Infections by this pathogen lead to a fatality rate that is higher than those seen with other RGM species. Infection of CF patients with M. abscessus is a major health-related issue in most CF centers worldwide (1, 2, 6, 7) and is considered a contraindication to lung transplantation, leaving these patients with minimal therapeutic options.M. abscessus provokes very challenging therapeutic issues because of its natural resistance to most available antibiotics (8-10) and is considered the most drug-resistant mycobacterial species. The lack of optimal therapeutic treatments and the emergence of multidrug resistance in M. abscessus stress the need for the discovery of new strategies to combat these infections.Reverse genetics, based on the comparison between pathogenic and nonpathogenic species, allows the identification of genes missing in nonpathogenic species and encoding potential virulence...

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DNA/Amphiphilic Block Copolymer Nanospheres Promote Low-dose DNA Vaccination

Cited by 33 publications

References 47 publications

Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

A nonviral pHEMA+chitosan nanosphere-mediated high-efficiency gene delivery system

MgtC as a Host-Induced Factor and Vaccine Candidate against Mycobacterium abscessus Infection

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