Linked Life Data

21418037

Source:http://linkedlifedata.com/resource/pubmed/id/21418037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-5-16
pubmed:abstractText
Phagocytic macrophages and dendritic cells are desirable targets for potential RNAi (RNA interference) therapeutics because they often mediate pathogenic inflammation and autoimmune responses. We recently engineered a complex 5 component glucan-based encapsulation system for siRNA (small interfering RNA) delivery to phagocytes. In experiments designed to simplify this original formulation, we discovered that the amphipathic peptide Endo-Porter forms stable nanocomplexes with siRNA that can mediate potent gene silencing in multiple cell types. In order to restrict such gene silencing to phagocytes, a method was developed to entrap siRNA-Endo-Porter complexes in glucan shells of 2-4 ?m diameter in the absence of other components. The resulting glucan particles containing fluorescently labelled siRNA were readily internalized by macrophages, but not other cell types, and released the labelled siRNA into the macrophage cytoplasm. Intraperitoneal administration of such glucan particles containing siRNA-Endo-Porter complexes to mice caused gene silencing specifically in macrophages that internalized the particles. These results from the present study indicate that specific targeting to phagocytes is mediated by the glucan, whereas Endo-Porter peptide serves both to anchor siRNA within glucan particles and to catalyse escape of siRNA from phagosomes. Thus we have developed a simplified siRNA delivery system that effectively and specifically targets phagocytes in culture or in intact mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
436
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-62
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Glucan particles for selective delivery of siRNA to phagocytic cells in mice.
pubmed:affiliation
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural