Development of targeted liposomal delivery systems for improved siRNA delivery to diseased endothelium.


Contact: Jan Kamps

 

Gene silencing by siRNA is capable of knocking down targets in various diseases in vivo, including in hypercholesterolaemia (1) and cancer (2).

Furthermore, siRNA technology enables generation of cell specific, gene specific knock out animal models to mimic human diseases (3). However, naked siRNA is unable to cross the cellular membrane, therefore significant effort is put into the development of suitable delivery systems (4). Liposomes are such systems which can be tailored on demand to introduce cell specificity and that did not show toxicity in clinical studies (5).

 

We designed and patented a system with superior intracellular release characteristics that is suitable for systemic application of siRNA (6,7). The aim of the research is the further development of SAINT-O-Somes in order to maximize in vitro and in vivo efficacy of siRNA delivery and gene down regulation in inflamed endothelial cells and endothelial cells that engage in angiogenesis. In addition to SAINT-O-Somes, our laboratory developed a lipid-based targeting device for siRNA delivery called SAINTargs, which efficiently and specifically deliver siRNA into endothelial cells (8). Current experiments focus on further development of SAINTargs for in vivo applications.

 

References :

1. Frank-Kamenetsky M et al., Proc Natl Acad Sci., 2008; 105 (33):11915-20

2. Takeshita Fet al., Proc Natl Acad Sci, 2005; 102(34):12177-82

3. Lee WC et al., Organogenesis, 2008; 4(3):176-81

4. Kowalski PS, Leus NG, Scherphof GL, Ruiters MH, Kamps JA, Molema G, IUBMB Life 2011; 63:648-58

5. Bartsch M, Weeke-Klimp AH, Meijer DK, Scherphof, GL,Kamps JA, J Liposome Res. 2005; 15(12):59-92

6. Joanna E. Adrian, Henriëtte W.M. Morselt, Regine Süss, Sabine Barnert, Jan Willem Kok, Sigridur A. Ásgeirsdóttir, Marcel H.J. Ruiters, Grietje Molema, Jan A.A.M. Kamps, J. Control Release 2010; 144(3):341-9

7. Kowalski PS, Lintermans LL, Morselt HW, Leus NG, Ruiters MH, Molema G, Kamps JA, Mol Pharm 2013; 10:3033-44

8. Leus NG, Talman EG, Ramana P, Kowalski PS, Woudenberg-Vrenken TE, Ruiters MH, Molema G, Kamps JA, Int J Pharm 2014; 459(1-2):40-50


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Ingrid (G.) Molema

Professor of Life Sciences / EBVDT Group Leader

University Medical Center Groningen (UMCG)

Dept. Pathology and Medical Biology, Medical Biology section

 

Room T2.228

Internal postal code: EA11

Hanzeplein 1

9713 GZ Groningen

The Netherlands

Telephone: +31-50-3610115

Fax: +31-50-3619911

Email: g.molema01@umcg.nl

 

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