In response to a question about the history of Vivo-Morpholino use in rodent livers, I assembled this annotated citation list.
Wu N, Meng F, Invernizzi P, Bernuzzi F, Venter J, Standeford H, Onori P, Marzioni M, Alvaro D, Franchitto A, Gaudio E, Glaser S, Alpini G. The secretin/secretin receptor axis modulates liver fibrosis through changes in TGF-β1 biliary secretion. Hepatology. 2016 Apr 26. doi: 10.1002/hep.28622. [Epub ahead of print]
This paper used Vivo-Morpholinos in a liver-related study, but I am not certain the molecular target was in the liver ( I do not have access to the full article).
Ray D, Han Y, Franchitto A, DeMorrow S, Meng F, Venter J, McMillin M, Kennedy L, Francis H, Onori P, Mancinelli R, Gaudio E, Alpini G, Glaser SS. Gonadotropin-releasing hormone stimulates biliary proliferation by paracrine/autocrine mechanisms. Am J Pathol. 2015 Apr;185(4):1061-72. doi: 10.1016/j.ajpath.2014.12.004.
"In separate experiments, BDL rats (immediately after surgery)2 were treated with Vivo-Morpholino sequences against GnRH (5′-GATCGTTTCCATTCTGTTTGGATGT-3′, 1.0 mg/kg body weight/day to reduce the hepatic GnRH expression) or mismatch-morpholino sequences (5′-GAACCTTTCGATTCTCTTTCGATGT-3′) administered by an implanted portal vein catheter for 1 week."
Gallego-Villar L, Viecelli HM, Pérez B, Harding CO, Ugarte M, Thöny B, Desviat LR. A sensitive assay system to test antisense oligonucleotides for splice suppression therapy in the mouse liver. Mol Ther Nucleic Acids. 2014 Sep 16;3:e193. doi: 10.1038/mtna.2014.44.
"Mice were injected with different amounts of VMO from 6 to 50 mg/kg body weight, using i.p. or i.v. injections."
Francis H, McDaniel K, Han Y, Liu X, Kennedy L, Yang F, McCarra J, Zhou T, Glaser S, Venter J, Huang L, Levine P, Lai J-M, Liu C-G, Alpini G, Meng F. Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver injury. J Biol Chem. 2014;[Epub ahead of print] doi:10.1074/jbc.M114.602383
"Furthermore, inhibition of miR-21 by specific Vivo-Morpholino and knockout of IL-6 in ethanol-treated mice also increased the expression of DR5 and FASLG in vivo during alcoholic liver injury."
Renzi A, Mancinelli R, Onori P, Franchitto A, Alpini G, Glaser S, Gaudio E. Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes. Hepatobiliary Surg Nutr. 2014;3(1):4-10. doi:10.3978/j.issn.2304-3881.2014.01.02
"We used normal and BDL rats that immediately after surgery were treated with Vivo-Morpholino sequences of AANAT or Morpholino mismatched (1 mg/kg BW/day) for one week via an implanted portal vein catheter as described by us (21). To minimize the amount of Vivo-Morpholino that circulates outside of the liver, we used a lower dose (1.0 mg/kg BW/day) (21) of Vivo-Morpholino than that used in a previous study (3.0 mg/kg/day)"
Glaser S, Meng F, Han Y, Onori P, Chow BK, Francis H, Venter J, McDaniel K, Marzioni M, Invernizzi P, Ueno Y, Lai JM, Huang L, Standeford H, Alvaro D, Gaudio E, Franchitto A, Alpini G. Secretin Stimulates Biliary Cell Proliferation by Regulating Expression of MicroRNA 125b and MicroRNA let7a in Mice. Gastroenterology. 2014 Feb 25. pii: S0016-5085(14)00241-8. doi: 10.1053/j.gastro.2014.02.030. [Epub ahead of print]
Two tail-vein injections at 30 mg/kg targeting microRNAs mmu-miR-125b or mmu-miR-let7
Lee TKW, Cheung VCH, Lu P, Lau EYT, Ma S, Tang KH, Tong M, Lo J, Ng IOL. Blockade of CD47 mediated CTSS-PAR2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology. 2014;[Epub ahead of print] doi:10.1002/hep.27070
Human xenograft in mice, intratumoral injection
Ramachandran A, McGill MR, Xie Y, Ni HM, Ding WX, Jaeschke H. The receptor interacting protein kinase 3 is a critical early mediator of acetaminophen-induced hepatocyte necrosis in mice. Hepatology. 2013 Dec;58(6):2099-108. doi: 10.1002/hep.26547. Epub 2013 Oct 11.
"In vivo morpholinos were used as supplied by the manufacturer and injected ip in mice at a dose of 12.5 mg/kg body weight every 24h for 2 days."
Frampton G, Ueno Y, Quinn M, McMillin M, Pae HY, Galindo C, Leyva-Illades D, Demorrow S. The novel growth factor, progranulin, stimulates mouse cholangiocyte proliferation via Sirtuin1-mediated inactivation of FOXO1. Am J Physiol Gastrointest Liver Physiol. 2012 Oct 18. [Epub ahead of print]
"In parallel, mice were injected with 10 mg/kg/day (via tail vein) PGRN165 specific Vivo-morpholino or a mismatched control sequence 24 hr prior to BDL or sham surgery. Daily tail vein injections of Vivo-morpholino sequences were continued for two days post surgery."
Renzi A, Demorrow S, Onori P, Carpino G, Mancinelli R, Meng F, Venter J, White M, Franchitto A, Francis H, Han Y, Ueno Y, Dusio G, Jensen KJ, Greene JJ, Glaser S, Gaudio E, Alpini G. Modulation of the biliary expression of arylalkylamine N-acetyltransferase alters the autocrine proliferative responses of cholangiocytes. Hepatology. 2012 Oct 18. doi: 10.1002/hep.26105. [Epub ahead of print]
"In separate experiments, healthy or BDL (immediately after surgery)2 rats (n = 9 per group) were treated with Vivo-Morpholino sequences of AANAT (5′-GTTCCCCAGCTTTGGAAGTGGTCCC, to reduce hepatic expression of AANAT) or mismatched Morpholino (5′-GTTCCCGACCTTTGCAACTCGTCCC) (Gene Tools LCC, Philomath, OR) for 1 week by an implanted portal vein catheter (Supporting Materials). Serum, liver tissue, cholangiocytes, pineal gland, kidney, spleen, small intestine, stomach, and heart were collected. Because we aimed to selectively knock down AANAT expression in the liver, we used a lower dose (1.0 mg/kg BW/day) of Vivo-Morpholino than that previously described (3.0 mg/kg/day).17 This approach minimizes the amount of Vivo-Morpholino that circulates outside of the liver after slow infusion into the portal vein."
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