γ-Polyglutamic acid-coated vectors for effective and safe gene therapy

Kurosaki, Tomoaki; Kitahara, Takashi; Kawakami, Shigeru; Higuchi, Yuriko; Yamaguchi, Ayumi; Nakagawa, Hiroo; Kodama, Yukinobu; Hamamoto, Tomoyuki; Hashida, Mitsuru; Sasaki, Hidetada

doi:10.1016/j.jconrel.2009.11.010

Cited by 86 publications

(56 citation statements)

References 33 publications

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“…Also, we found that γ-PGA complex was taken up by γ-PGA-specific receptormediated endocytotic pathway. 8,11) We discovered that the γ-PGA-coated complex showed high gene expression selectively in the marginal zone of the spleen (Figs. 2, 3).…”

Section: Discussionmentioning

confidence: 99%

Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

Kurosaki

Kodama

Muro

et al. 2013

Biological & Pharmaceutical Bulletin

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In this experiment, we developed a novel safe and effective gene delivery vector coated with γ-polyglutamic acid (γ-PGA-coated complexes). The γ-PGA-coated complex was composed of chiseled spherical nano-particles with anionic charges. The plasmid DNA/polyethyleneimine complex (non-coated complex) showed high transgene efficiency in the spleen and lung after intravenous administration in mice, with high liver toxicity and lethality. On the other hand, γ-PGA-coated complex selectively showed high transgene efficiency in the spleen without such toxicity. Furthermore, the γ-PGA-coated complex highly accumulated and showed high gene expression in the marginal zone of the spleen. Those results strongly indicated that γ-PGA-coated complex was suitable as a DNA vaccine vector. We therefore applied γ-PGA-coated complex to melanoma DNA vaccine, pUb-M. The γ-PGA-coated complex containing pUb-M significantly inhibited the growth and metastasis of a melanoma cell line, B16-F10 cells. In conclusion, we developed a splenic gene vector, γ-PGA-coated complex, as a novel technology for clinical vaccination.

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Section: Discussionmentioning

confidence: 99%

Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

Kurosaki

Kodama

Muro

et al. 2013

Biological & Pharmaceutical Bulletin

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“…1 Non-viral lipid carriers have been developed within recent years as an alternative to viral type gene vectors. They are mostly cationic lipid-based gene delivery systems which were developed as tools for gene delivery e.g., 2,3 (for a review see ref. 4 ).…”

Section: Introductionmentioning

confidence: 99%

Liposome-coated lipoplex–based carrier for antisense oligonucleotides

Wyrozumska

Meissner

Toporkiewicz

et al. 2014

Cancer Biology & Therapy

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fluorescent protein; HPC, hydrogenated egg phosphatidylcholine); pDNA, plasmid DNA; PE/PC, phosphatidylethanolamine and phosphatidylcholine liposomes; siRNA, small interferingRNA TGI, tumor growth inhibition.The chemical nature of genetic drugs (e.g. antisense oligonucleotides, siRNA, vectors) requires a suitable carrier system to protect them from enzymatic degradation without changing their properties and enable efficient delivery into target cells. Lipid vectors for nucleic acid delivery that have been widely investigated for years can be very effective. As the majority of attempts made in the field of cancer gene therapy have focused on solid tumors, while blood cancer cells have attracted less attention, the latter became the subject of our investigation. The lipid carrier proposed here is based on liposomes constructed by others but the lipid composition is original. A liposome-coated lipoplex (L-cL) consists of a core arising from complexation of positively charged lipid and negatively charged oligodeoxynucleotide (ODN) or plasmid DNA coated by a neutral or anionic lipid bilayer. Moreover, our lipid vector demonstrates size stability and is able to retain a high content of enclosed plasmid DNA or antisense oligodeoxynucleotides (asODNs). Observed transfection efficacies of the tested preparation using a plasmid coding for fluorescent protein were up to 60-85% of examined leukemia cells (Jurkat T and HL-60 lines) in the absence or the presence of serum. When BCL-2 asODN was encapsulated in the L-cL, specific silencing of this gene product at both the mRNA and protein level and also a markedly decreased cell survival rate were observed in vitro. Moreover, biodistribution analysis in mice indicates prolonged circulation characteristic for PEG-modified liposomal carriers. Experiments on tumor-engrafted animals indicate substantial inhibition of tumor growth.

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“…Various physicochemical and biological differences based on their different side chains have been reported to affect their affinity for nucleic acids and the resultant polyplex structures [4,5]. The transfection efficiency of PR is higher than that of PK [6,7], and whether this disparity is due to the difference in their affinities or polyplex structures remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Quantitative comparison between poly(L-arginine) and poly(L-lysine) at each step of polyplex-based gene transfection using a microinjection technique

Hashimoto

Kawazu

Nagasaki

et al. 2012

Science and Technology of Advanced Materials

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Among the well-studied polypeptide-type gene carriers, transfection efficiency is empirically known to be higher for poly(L-arginine) (PR) than poly(L-lysine) (PK). The big difference between PR and PK should be determined at one of the intracellular trafficking steps based on the different charge densities, structures or PKa values. However, the endosomal escape and the intranuclear transcription efficiency in living cells have not been clarified yet. In this study, a novel method for quantifying the intranuclear transcription efficiency and the nuclear transport of the polyplex is established based on the nuclear and the cytosolic microinjection technique, and the results for PK and PR with different molecular weights (MWs) are compared in living cells. The intranuclear transcription efficiency is the same in PR and PK and it decreases rapidly with increasing MW, in spite of the commonly measured transfection efficiency. The transcription efficiency is strongly suppressed at high MW and strongly correlates with the polyplex forming ability expressed as a critical ratio of the number of polypeptide cationic groups to the number of pDNA anionic groups. When considered with the results of the cellular uptake and in vitro transfection with or without chloroquine, the rate-limiting step for their gene transfer is the buffering effect-independent endosomal escape.

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γ-Polyglutamic acid-coated vectors for effective and safe gene therapy

Abstract: In the present study, we developed some novel gene delivery vectors, coated cationic complexes with γ-polyglutamic acid (γ-PGA) for effective and safe gene therapy. Cationic

Cited by 86 publications

References 33 publications

Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine

Liposome-coated lipoplex–based carrier for antisense oligonucleotides

Quantitative comparison between poly(L-arginine) and poly(L-lysine) at each step of polyplex-based gene transfection using a microinjection technique

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