Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

Enhanced cell delivery and biological activity of anti-sense nucleic acids and short interference RNA by conjugation with cell penetrating peptides

New chemistry methods were developed for the conjugation of CPPs to a range of to gene modulating steric blocking anti-sense oligonucleotides, PNA and short interference RNA, aimed at obviating the need for cell transfection agents. CPP conjugation often enhanced uptake of such cargoes into cultured cells but uptake amount varied depending on the types of CPP and cargo. Conjugates were found predominantly in endosomal or membrane bound compartments. Steric block cargoes were tested in a model HIV-1 Tat-dependent trans-activation system, where activity is attained only if the cargo enters the cell nucleus and binds an RNA target (TAR).

Activity was found only for certain disulfide linked PNA-CPP conjugates delivered for 24h at µM concentrations, demonstrating that release into cytosol and nucleus is extremely difficult and structure-dependent. Activities could often be enhanced by co-administration of the endosomal release reagent chloroquine. CPPs disulfide-linked to siRNA in some cases were able to elicit reductions in expression of target p38 MAP kinase when incubated at µM concentrations with cells. The results are not yet advanced enough for commercial or medical application, but will guide future research into a) PNA-peptide conjugates for gene correction of splicing and as potential antiviral agents, and b) cell and mouse lung delivery of siRNA.

Información relacionada

Reported by

Medical Research Council
MRC Laboratory of Molecular Biology, Hills Road
CB2 0QH Cambridge
United Kingdom
See on map
Síganos en: RSS Facebook Twitter YouTube Gestionado por la Oficina de Publicaciones de la UE Arriba