Effectiveness of siRNA uptake in target tissues by various delivery methods.
BACKGROUND
RNA interference offers clinical potential as a therapeutic modality for a variety of diseases; the efficacy of in vivo delivery remains poorly understood. The purpose of our study was to compare and contrast short interfering RNA (siRNA) uptake in vivo using various delivery techniques.


METHODS
DY547- and rhodamine-labeled siRNA was administered to mice by one of four delivery methods: (1) hydrodynamic intravenous tail vein injection, (2) standard intravenous tail vein injection, (3) intraperitoneal injection, and (4) rectal administration. Mice were killed over a time course; representative tissue samples were collected and analyzed using fluorescent microscopy to determine siRNA uptake.


RESULTS
siRNA uptake was noted in the liver, kidney, pancreas, spleen, and bone marrow by both hydrodynamic and standard IV injection. siRNA uptake was detected in the spleen, liver, and bone marrow after intraperitoneal administration. Rectal administration resulted in siRNA uptake in the spleen, bone marrow, and colon.


CONCLUSIONS
Our results demonstrate differential siRNA uptake depending on delivery technique. Importantly, our results demonstrate the potential of siRNA as a systemic therapeutic option in vivo for selected disease processes.
Larson
Shawn D
SD
Department of Surgery, The University of Texas Medical Branch, Galveston, Tex, USA.
Jackson
Lindsey N
LN
Chen
L Andy
LA
Rychahou
Piotr G
PG
Evers
B Mark
BM
D000818:Animals; D001853:Bone Marrow; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney; D008099:Liver; D051379:Mice; D010179:Pancreas; D034741:RNA, Small Interfering / Q000493:pharmacokinetics*; D012007:Rectum; D013154:Spleen; D013623:Tail / Q000098:blood supply; D014018:Tissue Distribution
D034741:RNA, Small Interfering
Nature. 2001 May 24;411(6836):494-8
11373684
Clin Cancer Res. 2002 Jun;8(6):1940-7
12060639
Nature. 2002 Jul 4;418(6893):38-9
12097900
Cancer Cell. 2002 Sep;2(3):243-7
12242156
J Mol Biol. 2003 Apr 4;327(4):761-6
12654261
Mol Vis. 2003 May 30;9:210-6
12789138
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7797-802
12810955
Bioorg Med Chem Lett. 2004 Mar 8;14(5):1139-43
14980652
Nucleic Acids Res. 2004;32(5):e49
15026538
Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8682-6
15173583
Anal Biochem. 1976 May 7;72:248-54
942051
Nature. 1998 Feb 19;391(6669):806-11
9486653
Nature. 2004 Nov 11;432(7014):173-8
15538359
Nat Med. 2005 Jan;11(1):56-62
15619625
Nat Med. 2005 Jan;11(1):50-5
15619632
Gene Ther. 2005 Mar;12(5):461-6
15616603
Transplant Proc. 2005 Jan-Feb;37(1):233-6
15808605
Gastroenterology. 2005 May;128(5):1391-404
15887120
Cancer Res. 2005 Aug 1;65(15):6910-8
16061675
FEBS Lett. 2005 Oct 31;579(26):5996-6007
16115631
Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L405-13
16183667
Ann Surg. 2006 Jun;243(6):833-42; discussion 843-4
16772787
Mol Ther. 2006 Sep;14(3):336-42
16766229
Cell Cycle. 2006 Sep;5(18):2103-9
16940756
Surgery. 2006 Nov;140(5):719-25
17084714