Reference - Detail
| RRC ID | 45191 |
|---|---|
| Author | Anno T, Higashi T, Hayashi Y, Motoyama K, Jono H, Ando Y, Arima H. |
| Title | Potential use of glucuronylglucosyl-β-cyclodextrin/dendrimer conjugate (G2) as a siRNA carrier for the treatment of familial amyloidotic polyneuropathy. |
| Journal | J Drug Target |
| Abstract |
We previously reported that 6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin (GUG-β-CyD) conjugate with polyamidoamine dendrimer (dendrimer, generation 2; G2) (GUG-β-CDE (G2)) is useful as a gene transfer carrier. In the present study, to investigate the potentials of GUG-β-CDE (G2) as a siRNA carrier, we evaluated the RNAi effect of its complex with siRNA against transthyretin (TTR) mRNA (siTTR) for the treatment of familial amyloidotic polyneuropathy (FAP). Among the various GUG-β-CDEs (G2) having the different degrees of substitution of GUG-β-CyD (degree of substation (DS) 1.8, 2.5, 3.0 and 5.0), GUG-β-CDE (G2, DS 1.8) showed the highest siTTR transfer activity. GUG-β-CDE (G2, DS 1.8)/siTTR complex showed no cytotoxicity in HepG2 cells. After intravenous administration of GUG-β-CDE (G2, DS 1.8)/siTTR complex to BALB/c mice, TTR mRNA expression was tended to reduce with negligible change of blood chemistry data. Particle size, ζ-potential and cellular association of the GUG-β-CDE (G2, DS 1.8) complex were almost the same as those of the other CDEs complexes. Meanwhile, GUG-β-CDE (G2, DS 1.8)/siTTR complex showed high endosomal escaping ability of siTTR in cytoplasm. These findings suggest the potential of GUG-β-CDE (G2, DS 1.8) as a siRNA carrier for the FAP treatment. |
| Volume | 22(10) |
| Pages | 883-90 |
| Published | 2014-12-1 |
| DOI | 10.3109/1061186X.2014.939984 |
| PMID | 25051178 |
| MeSH | Administration, Intravenous Amyloid Neuropathies, Familial / genetics Amyloid Neuropathies, Familial / therapy* Animals Dendrimers / chemistry* Endosomes / metabolism Gene Transfer Techniques Hep G2 Cells Humans Male Mice Mice, Inbred BALB C Oligosaccharides / chemistry* Particle Size Polyamines / chemistry* Prealbumin / genetics RNA, Messenger / metabolism RNA, Small Interfering / administration & dosage* |
| IF | 3.38 |
| Times Cited | 9 |
| WOS Category | PHARMACOLOGY & PHARMACY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Hep G2 |