Design and creation of new nanomaterials for therapeutic RNAi

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Life Sciences | Medicine and Health Sciences


RNA interference is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies needs to overcome two barriers and be able to (i) identify chemically stable and effective siRNA sequences and (ii) efficiently silence target genes with siRNA doses that will be clinically feasible in humans. Here, we report the design and creation of interfering nanoparticles (iNOPs) as new systemic gene-silencing agents. iNOPs have two subunits: (i) a well-defined functionalized lipid nanoparticle as a delivery agent and (ii) a chemically modified siRNA for sustained silencing in vivo. When we injected iNOPs containing only 1-5 mg kg(-1) siRNA into mice, an endogenous gene for apolipoprotein B (apoB) was silenced in liver, plasma levels of apoB decreased, and total plasma cholesterol was lowered. iNOP treatment was nontoxic and did not induce an immune response. Our results show that these iNOPs can silence disease-related endogenous genes in clinically acceptable and therapeutically affordable doses.

DOI of Published Version



ACS Chem Biol. 2007 Apr 24;2(4):237-41. Link to article on publisher's site

Journal/Book/Conference Title

ACS chemical biology

Related Resources

Link to Article in PubMed

PubMed ID