Enhanced intracellular delivery and multi-target gene silencing triggered by tripodal RNA structures.
BACKGROUND
The development of gene interfering RNA (iRNA) molecules such as small interfering RNAs (siRNAs) and antagomirs provides promising therapeutic modalities for targeting specific mRNAs and microRNAs (miRNAs) involved in disease mechanisms. Therapeutic iRNA strategy against cancer or hypermutable viruses prefers targeting multiple genes simultaneously to achieve synergistic inhibition and to prevent resistance.


METHODS
In the present study, we report chemically synthesized, multi-target gene interfering RNA structures based upon branched, tripodal interfering RNAs (termed T-tiRNAs).


RESULTS
The T-tiRNAs could simultaneously inhibit up to three different mRNAs or miRNAs by harboring three siRNA or antagomir units. Moreover, when complexed with cationic delivery vehicles, T-tiRNAs showed enhanced gene interfering activity over conventional siRNAs or antagomirs as a result of increased intracellular delivery.


CONCLUSIONS
The data obtained in the present study provide an example of synthetic multi-functional RNA structures that enable multiple gene interference in mammalian cells, which could become powerful tools for an efficient combinatorial iRNA strategy.
Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea.
Chan Il
CI
Chang
Tae Yeon
TY
Lee
Sera
S
Kim
Xiangao
X
Sun
Sun Woo
SW
Hong
Jae Wook
JW
Yoo
Pooja
P
Dua
Hye Suk
HS
Kang
Soyoun
S
Kim
Chiang J
CJ
Li
Dong-Ki
DK
Lee
D005434:Flow Cytometry; D020868:Gene Silencing / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D011094:Polyethyleneimine; D012313:RNA / Q000737:chemistry*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA; D011094:Polyethyleneimine; D008156:Luciferases