Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Harada-Shiba, M. et al.

Mariko Harada-Shiba, Itaru Takamisawa, Kanjiro Miyata, Takehiko Ishii, Nobuhiro Nishiyama, Keiji Itaka, Kenji Kangawa, Fumiki Yoshihara, Yujiro Asada, Kinta Hatakeyama, Noriya Nagaya, Kazunori Kataoka,

Intratracheal gene transfer of adrenomedullin using polyplex nanomicelles attenuates monocrotaline-induced pulmonary hypertension in rats.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive PAH and right ventricular failure. Despite recent advances in therapeutic approaches using prostanoids, endothelin antagonists, and so on, PAH remains a challenging condition. To develop a novel therapeutic approach, we have established a nonviral gene delivery system of poly(ethylene glycol) (PEG)-based block catiomers, which form a polyplex nanomicelle with a nanoscaled core-shell structure in the presence of DNA. The polyplex nanomicelle from PEG-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-P[Asp(DET)]), having ethylenediamine units at the side chain, showed ~100-fold increase in luciferase transgene expression activity in mouse lung via intratracheal administration with a minimal toxicity compared with the polyplex from linear poly(ethylenimine) (LPEI). The transfection activity was highest on day 3 after administration and remained detectable until day 14. PEG-b-P[Asp(DET)] polyplex nanomicelles were formulated with a therapeutic plasmid bearing the human adrenomedullin (AM) gene and intratracheally administered to rats with monocrotaline-induced pulmonary hypertension. The right ventricular pressure significantly decreased 3 days after administration as confirmed by a notable increase of pulmonary human AM mRNA levels. Intratracheal administration of PEG-b-P[Asp-(DET)] polyplex nanomicelles showed remarkable therapeutic efficacy with PAH animal models without compromising biocompatibility.[1]

References

Intratracheal gene transfer of adrenomedullin using polyplex nanomicelles attenuates monocrotaline-induced pulmonary hypertension in rats. Harada-Shiba, M., Takamisawa, I., Miyata, K., Ishii, T., Nishiyama, N., Itaka, K., Kangawa, K., Yoshihara, F., Asada, Y., Hatakeyama, K., Nagaya, N., Kataoka, K. Mol. Ther. (2009) [Pubmed]

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