RGD Reference Report - Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. - Rat Genome Database

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Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes.

Authors: Kim, Gyeungyun  Kim, Minkyung  Lee, Youngki  Byun, Jung Woo  Hwang, Do Won  Lee, Minhyung 
Citation: Kim G, etal., J Control Release. 2020 Jan 10;317:273-281. doi: 10.1016/j.jconrel.2019.11.009. Epub 2019 Nov 12.
RGD ID: 41404645
Pubmed: PMID:31730913   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jconrel.2019.11.009   (Journal Full-text)

Antisense miRNA oligonucleotides against miR-21 (AMO-21) have a therapeutic potential for treatment of glioblastoma. However, glioblastoma-targeted delivery through systemic injection requires development of an efficient targeting carrier. For this purpose, a glioblastoma-targeting carrier was developed using the T7 peptide and exosomes. The transferrin receptor is overexpressed on the surface of glioblastoma cells, and T7 is a transferrin receptor-binding peptide. A T7 peptide-decorated exosome (T7-exo) was produced by incorporation of T7 into the exosome membrane as a fusion protein of T7 and Lamp2b. As a control, rabies virus glycoprotein (RVG) peptide targeting brain neuron cells was incorporated into the exosome membrane. AMO-21 was loaded into the exosomes by electroporation. In vitro studies of AMO-21 delivery showed that T7-exo had a higher delivery efficiency to C6 glioblastoma cells than unmodified exosome (Unmod-exo) and RVG-decorated exosome (RVG-exo). For in vivo delivery studies, T7-exo with AMO-21 was delivered into intracranial glioblastoma rat models by intravenous injection through the tail vein. The results showed that T7-exo delivered AMO-21 into the brain more efficiently than Unmod-exo and RVG-exo. In addition, delivery of AMO-21 using T7-exo reduced the miR-21 level in the glioblastoma efficiently. Reduction of miR-21 by AMO-21 induced the expression of PDCD4 and PTEN in tumors, resulting in reduction of tumor sizes. Taken together, these findings indicate that T7-exo is an efficient carrier of AMO-21 into the glioblastoma and may be useful in development of glioblastoma therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glioblastoma amelioratesISOMir21 (Rattus norvegicus)41404645; 41404645 RGD 
glioblastoma amelioratesIMP 41404645 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)


Additional Information