title: Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth.
abstract: PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential of this approach by using small interfering RNA (siRNA) encapsulated by lipid nanoparticles. Therapy experiments of PCTAIRE1 siRNA were performed using human HCT116 colorectal cancer cells and human A2058 melanoma cells. A single dose of PCTAIRE1 siRNA-lipid nanoparticles was found to be highly effective in reducing in vivo PCTAIRE1 expression for up to 4 days as assayed by immunoblotting. Therapy experiments were started 4 days after subcutaneous injection of cancer cells. Treatment with PCTAIRE1 siRNA-lipid nanoparticles (0.5 mg/kg RNA, twice a week) reduced tumor volume and weight significantly compared with the scramble-control group. Histopathological analysis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) showed increased apoptosis of tumor cells treated with PCTAIRE1-siRNA. Overall, our results demonstrate that siRNA treatment targeting PCTAIRE1 is effective in vivo, suggesting that PCTAIRE1 siRNA-lipid nanoparticles might be a novel therapeutic approach against cancer cells.
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.|Current address: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Yanagi
authors.affiliation: Arcturus Therapeutics Inc., San Diego, California, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Tachikawa
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.|Arcturus Therapeutics Inc., San Diego, California, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wilkie-Grantham
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.
authors.forename: Asami
authors.initials: A
authors.lastname: Hishiki
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.
authors.forename: Ko
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Toyonaga
authors.affiliation: Arcturus Therapeutics Inc., San Diego, California, USA.
authors.forename: Pad
authors.initials: P
authors.lastname: Chivukula
authors.affiliation: Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.|Current address: Department of Neurology, Kyoto University Graduate School of Medicine Kyoto, Japan.
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Matsuzawa