Manipulation of local disposition and gene expression characteristics of plasmid DNA following intramuscular administration by complexation with cationic macromolecule

Kawase, Atsushi; Kobayashi, Naoki; Isaji, Keiko; Nishikawa, Makiya; Takakura, Yoshinobu

doi:10.1016/j.ijpharm.2004.12.011

Cited by 6 publications

(7 citation statements)

References 22 publications

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“…proteoglycans) in the extracellular matrix that may strongly interact with these complexes and hinder their mobility in the tissue. 30,31,32 Whether or not this property is desired is dependent on the context of the DNA delivery system—as it has been suggested that a depot formation may be advantageous in inducing sustained expression of antigens in non-viral DNA vaccines, 1,4,33 while others have showed that reducing the cationic surface charge can improve the distribution, and thereby promote transfection, to cells other than those found at the injection site ( i.e. , transfection of both APCs and local dermal cells).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been well established that the composition, size, and surface charge of a complex can govern its distribution to different tissues in vivo. 1,2,3,4 More subtle differences, such as the chain length of the DNA-condensing polymer, can also influence the distribution of the complex to different organs in mice, and in turn, affect transfection efficiency. 5,6 Accurate determination of the absolute mass of plasmid distributed to different tissue sites is critical to studies of the mechanisms of action of gene delivery systems and understanding the influence of the physicochemical properties of DNA complexes on their biological activity.…”

Section: Introductionmentioning

confidence: 99%

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Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

White

Pouton

2016

Molecular Therapy - Nucleic Acids

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Analysis of the tissue distribution of plasmid DNA after administration of nonviral gene delivery systems is best accomplished using quantitative real-time polymerase chain reaction (qPCR), although published strategies do not allow determination of the absolute mass of plasmid delivered to different tissues. Generally, data is expressed as the mass of plasmid relative to the mass of genomic DNA (gDNA) in the sample. This strategy is adequate for comparisons of efficiency of delivery to a single site but it does not allow direct comparison of delivery to multiple tissues, as the mass of gDNA extracted per unit mass of each tissue is different. We show here that by constructing qPCR standard curves for each tissue it is possible to determine the dose of intact plasmid remaining in each tissue, which is a more useful parameter when comparing the fates of different formulations of DNA. We exemplify the use of this tissue-specific qPCR method by comparing the delivery of naked DNA, cationic DNA complexes, and neutral PEGylated DNA complexes after intramuscular injection. Generally, larger masses of intact plasmid were present 24 hours after injection of DNA complexes, and neutral complexes resulted in delivery of a larger mass of intact plasmid to the spleen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

White

Pouton

2016

Molecular Therapy - Nucleic Acids

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“…[55,[165][166][167][168] In case of proteins such as albumin, methyl esterification of carboxyl groups decreases negative charge and renders the overall protein positively charged and well-suited for DNAc ondensation. [169] Alternatively,hydrophobic attraction can be employed to attach pDNAonto the carrier.T oachieve this,pDNAcan be hydrophobised with cetrimonium bromide [170] or dioleoyl-3trimethylammonium propane. [98,[171][172][173] Theadvantage of such an approach is that the carrier material is not only limited to positively charged polymers,b ut expands the scope to…”

Section: Polysaccharidesmentioning

confidence: 99%

Biopolymer‐based Carriers for DNA Vaccine Design

et al. 2021

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She studied chemistry at the University of Zagreb, and completed her PhD at the University of Strathclyde,G lasgow,w orking on DNA detection by advanced spectroscopies, such as SERRS. After postdoc research on DNA nanostructuring and artificial enzyme design at the University of Dortmund,s he was agroup leader at Karlsruhe Institute of Technology before joining Cambridge. Her research focuses on nanostructured biomaterials for use in photocatalysis and targeted drug delivery.

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“…When antigen peptides are bound or conjugated to Hsp70, the internalized peptides can be processed and presented on MHC molecules. 18,19) このアプローチでは，プラスミド DNA を mBSA と複合体化することで樹状細胞への遺伝子導入が増大することが可能であった (Fig. 4 (A)) ．その一方で，マウス筋肉内に投与したときの遺伝子発現は複合体化により大幅に減少した (Fig.…”

Section: Roles Of Hsp70 In Immune Responseunclassified

Development of Heat Shock Proteins with Controlled Distribution Properties and Their Application to Vaccine Delivery

2007

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Antigen delivery to antigen-presenting cells (APCs) is a key issue in developing eŠective cancer vaccines. Controlling the tissue distribution of antigens, which are administered in a peptide/protein or DNA form, can increase antigenspeciˆc immune responses, including the induction of cytotoxic T lymphocytes. Heat-shock protein 70 (Hsp70), a member of a highly conserved family of molecular chaperones, forms complexes with a variety of tumor-related antigens via its polypeptide binding domain. Because Hsp70 is taken up by APCs through the recognition by Hsp receptors, such as CD91 and LOX-1, its application to antigen delivery systems has been examined both in experimental and clinical settings. A tissue distribution study revealed that Hsp70 is mainly taken up by the liver, especially by hepatocytes, after intravenous injection in mice. A signiˆcant amount of Hsp70 was also delivered to regional lymph nodes when it was injected subcutaneously, supporting the hypothesis that Hsp70 is a natural targeting system to APCs. Model antigens were complexed with or conjugated to Hsp70, by which greater antigen-speciˆc immune responses were achieved. Cytoplasmic delivery of Hsp70-antigen further increased the e‹cacy of the Hsp70-based vaccines. Theseˆndings indicate that eŠective cancer therapy can be achieved by developing Hsp70-based anticancer vaccines when their tissue and intracellular distribution is properly controlled.

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Manipulation of local disposition and gene expression characteristics of plasmid DNA following intramuscular administration by complexation with cationic macromolecule

Cited by 6 publications

References 22 publications

Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

Biopolymer‐based Carriers for DNA Vaccine Design

Development of Heat Shock Proteins with Controlled Distribution Properties and Their Application to Vaccine Delivery

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