Carbonate apatite-facilitated intracellularly delivered siRNA for efficient knockdown of functional genes

Sharif Hossain, Anthony Stanislaus, Ming Jang Chua, Seiichi Tada, Yoh ichi Tagawa, Ezharul Hoque Chowdhury, Toshihiro Akaike

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

Abstract

Gene therapy through intracellular delivery of a functional gene or a gene-silencing element is a promising approach to treat critical diseases. Elucidation of the genetic basis of human diseases with complete sequencing of human genome revealed many vital genes as possible targets in gene therapy programs. RNA interference (RNAi), a powerful tool in functional genomics to selectively silence messenger RNA (mRNA) expression, can be harnessed to rapidly develop novel drugs against any disease target. The ability of synthetic small interfering RNA (siRNA) to effectively silence genes in vitro and in vivo, has made them particularly well suited as a drug therapeutic. However, since naked siRNA is unable to passively diffuse through cellular membranes, delivery of siRNA remains the major hurdle to fully exploit the potential of siRNA technology. Here pH-sensitive carbonate apatite has been developed to efficiently deliver siRNA into the mammalian cells by virtue of its high affinity interactions with the siRNA and the desirable size of the resulting siRNA/apatite complex for effective cellular endocytosis. Moreover, following internalization by cells, siRNA was found to be escaped from the endosomes in a time-dependent manner and finally, more efficiently silenced reporter genes at a low dose than commercially available lipofectamine. Knockdown of cyclin B1 gene with only 10. nM of siRNA delivered by carbonate apatite resulted in the significant death of cancer cells, suggesting that the new method of siRNA delivery is highly promising for pre-clinical and clinical cancer therapy.

Original languageEnglish
Pages (from-to)101-108
Number of pages8
JournalJournal of Controlled Release
Volume147
Issue number1
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer cell
  • Carbonate apatite
  • Cyclin B1
  • Gene silencing
  • SiRNA

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