DNA-cationic lipid complexation:

The development in gene therapy has caused a need for efficient transfection vectors. Viruses have been used in transfection several years. During resent years cationic liposomes have begun to be a rival for viruses due to several advantages, for example nonimmunogenity, low toxicity and capability to carry large amount of the DNA [1-3]. Still the properties of the cationic liposomes and the interaction between the DNA is not known accurately [1, 3]. The knowledge of these complexes also known as lipoplexes is mainly based on experimental results. There are a lot of data describing different kinds of biophysical properties of the systems [4-7]. Some theoretical research has also been done. The aim of these studies has been to achieve models to describe the interaction energy and the way of interaction between the DNA and a lipid bilayer or a lipid monolayer [8-10].

In the computational studies the lipid bilayer has been simulated by using the Monte Carlo method or Molecular Dynamics [11-13]. Simulations were made with lipid bilayer, which was in a water box during the simulations [12, 13]. The effect of the cationic lipid and the DNA was also studied [11].

In vivo experiments [14, 15] have shown that clinical applications of the DNA-cationic lipid complexes are effective and safe. Although there are still several unknown factors affecting the clinical use of these complexes.

In our research we study the properties of a monolayer which consists of zwitterionic and cationic lipids. We are using Monte Carlo and molecular dynamics simulations to help to understand the interactions in the experimental system and also the processes, which take place during the experiment.

Our cationic lipid and DNA related publications:

• Cationic DMPC/DMTAP Lipid Bilayers: Molecular Dynamics Study,
  A.A. Gurtovenko, Michael Patra, Mikko Karttunen, and Ilpo Vattulainen
  Biophys. J. 86, 3461-3472 (2004).
  [online]     [cond-mat/0312400]
  Download equilibrium configuration and parameters
  Selected in July 2004 issue of Molecular Modeling & Computational Chemistry (MMCC)

• Characterization of Sphingosine-Phosphatidylcholine Monlayers: Effects of DNA, V. Matti J. Säily, Juha-Matti Alakoskela, Samppa J. Ryhänen, Mikko Karttunen, and Paavo K.J. Kinnunen
  Langmuir 19, 8956-8963 (2003)
  [Online]

• Computational modeling of DNA-cationic lipid complexation,
  Mikko Karttunen, Antti L. Pakkanen, Paavo K.J. Kinnunen, and Kimmo Kaski,
  Cell. Mol. Biol. Lett., 7, 238 (2002).

• See our publication list.

General references:

1. M. S. Spector, J. M. Schnur, Science 275 (1997) 791-792
   
2. T. Paukku, S. Lauraeus, I. Huhtaniemi, P. K. J. Kinnunen, Chemistry and Physics of Lipids 87 (1997) 23-29
   
3. P. L. Felgner, T. R. Gadek, M. Holm, R. Roman, H. W. Chan, M. Wenz, J. P. Northrop, G. M. Ringold, M. Danielsen, Proceedings of the National Academy of Sciences of the United States of America 84 (1987) 7413-7417
   
4. J. Zabner, A. J. Fasberder, T. Moniger, K. A. Poellinger, M. J. Welsh, The Journal of Biological Chemistry 270 (1995) 18997-19007
   
5. R. Zantl, L. Baicu, F. Artzner, I. Sprenger, G. Rapp, J. O. Rädler, Journal of Physical Chemistry B 103 (1999) 10300-10310
   
6. P. G. Scherer, J. Seelig, Biochemistry 28 (1989) 7720-7728
   
7. J. Seelig, P. M. Macdonald, P. G. Scherer, Biochemisry 26 (1987) 7535-7541
   
8. N. Dan, Biophysical Journal 73 (1997) 1842-1846
   
9. S. May, D. Harries, A. Ben-Shaul, Biophysical Journal 78 (2000) 1681-1697
   
10. W. M. Gelbart, R. F. Bruinsma, P. A. Pincus, V. A. Parsegian, Physics Today 53 (2000) 38-44
    
11. S. Badhyopadhyay, M. Tarek, M. L. Klein, The Journal of Physical Chemistry B 103 (1999) 10075-10080
    
12. S. W. Chiu, E. Jakobsson, S. Subramaniam, H. L. Scott, Biophysical Journal 77 (1999) 2462-2469
    
13. P. Jedlovszky, M. Mezei, Journal of Chemical Physics 111 (1999) 10770-10773
    
14. E. W. f. W. Alton, M. Stern, R. Farley, A. Jaffe, S. L. Chadwick, J. Phillips, J. Davies, S. N. Smith, J. Browning, M. G. Davies, M. E. Hodson, S. R. Durham, D. Li, P. K. Jeffery, M. Scallan, R. Balfour, S. J. Eastman, S. H. Cheng, A. E. Smith, D. Meeker, D. M. Geddes, The Lancet 353 (1999) 947-954
    
15. N. J. Caplen, E. W. F. W. Alton, P. G. Middleton, J. R. Dorin, B. J. Stevenson, X. Gao, S. R. Durham, P. K. Jefery, M. E. Hodson, C. Coutelle, L. Huang, D. J. Porteous, R. Williamson, D. M. Geddes, Nature Medicine 1 (1995) 39-46