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Development of novel therapeutic approach using gene delivery method for treatment of cardiovascular disease

Novel therapeutic approach using nucleic acid drug and gene delivery method have been developed for the treatment of cardiovascular disease including familial hypercholesterolemia and pulmonary arterial hypertension.

In order to develop the novel non-viral method for gene delivery, polyion complex nanomicelles have been used under the collaboration with Professor Kazunori Kataoka (Univ. of Tokyo). We have reported the therapeutic effect of intratracheal administration of adrenomedullin by using PEG-PAsp(DET) in model animals of pulmonary arterial hypertension. This method for gene delivery was shown to be safe compared with that using viral vector. Our gene delivery method can be applied to the treatment of other diseases.

References

  1. Uchida S, Itaka K, Chen Q, Osada K, Ishii T, Shibata MA, Harada-Shiba M, Kataoka K: PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses: Mol Ther, 2012; 20(6): 1196-1203.
  2. Uchida S, Itaka K, Chen Q, Osada K, Miyata K, Ishii T, Harada-Shiba M, Kataoka K: Combination of chondroitin sulfate and polyplex micelles from Poly(ethylene glycol)-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} block copolymer for prolonged in vivo gene transfection with reduced toxicity: J Control Release, 2011; 155(2): 296-302.
  3. 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: Intratracheal gene transfer of adrenomedullin using polyplex nanomicelles attenuates monocrotaline-induced pulmonary hypertension in rats. Mol Ther 17: 1180-1186, 2009.
  4. Harada-Shiba M, Yamauchi K, Harada A, Takamisawa I, Shimokado K, Kataoka K: Polyion complex micelles as vectors in gene therapy--pharmacokinetics and in vivo gene transfer. Gene Ther 9: 407-414, 2002.
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