Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA.

ABSTRACT: The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis of complement factors does not reveal any changes tha

SUBMITTER: Heidel JD 

PROVIDER: S-EPMC1829492 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature