Enteral siRNA delivery technique for therapeutic gene silencing in the liver via the lymphatic route.
Sci Rep
; 5: 17035, 2015 Nov 23.
Article
in En
| MEDLINE
| ID: mdl-26593819
ABSTRACT
An efficient targeting delivery technology is needed for functional oligonucleotides to exert their potential effect on the target gene without an adverse effect in vivo. Development of enteral delivery systems for nucleic acids is a major challenge because of their large molecular size and instability. Here, we describe a new enteral delivery technique that enables small interfering RNA (siRNA) selectively delivered to the liver to silence its target Apolipoprotein B gene expression. A nuclease-resistant synthetic siRNA was conjugated with α-tochopherol and administered as lipid nanoparticle to the large intestine of the mice in a postprandial state. The selective transport into the liver, effective gene silence, and consequently significant reduction in serum low density lipoprotein-cholesterol level, were demonstrated. The chylomicron-mediated pathway via the lymphatic route was suggested as major mechanism. This unique approach may provide a basis for developing oral and rectal delivery systems for nucleic acids targeting liver.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organophosphorus Compounds
/
Apolipoproteins B
/
Drug Delivery Systems
/
Gene Silencing
/
RNA, Small Interfering
/
Nanoparticles
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2015
Document type:
Article
Affiliation country:
Japón