Abstract
Viral vector systems are the most commonly used gene transfer tools for clinical gene therapy. However, lipofection systems are potential alternatives because of lower immunogenicity and easier cGMP production, but in vivo stability and transduction efficacy need to be improved. Therefore, we investigated gene transduction efficiency of our novel cGMP cationic lipids, CCQ22 and CCQ32, by FACS analysis. Toxicity analysis was performed to determine the cytotoxic side effects of the novel lipids. To evaluate the stability of the compounds in the context of local delivery to patients with intraperitoneally metastatic ovarian cancer, gene transfer was also tested in the presence of malignant ascites. Our novel cGMP standard lipids mediated gene transfer rates of more than 50%. However, for most cell lines cytotoxic side effects were similar to our reference lipofection system. In general, ascites had no major influence on gene transduction rates with the novel lipids. Our results suggest that CCQs may compare favorably with commercially available lipofection systems. These promising results facilitate further analysis of the compounds.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Haines AMR, Irvine AS, Mountain A, et al. CL22 — a novel cationic peptide for efficient transfection of mammalian cells. Gene Ther. 2001;8:99–110.
Madry H, Trippel SB . Efficient lipid-mediated gene transfer to articular chondrocytes. Gene Ther. 2000;7:286–291.
Keil O, Bojar H, Prisack HB, Dall P . Novel lipophilic chloroquine analogues for a highly efficient gene transfer into gynecological tumors. Bioorg Med Chem Lett. 2001;11:2611–2613.
Yamazaki Y, Nango M, Matsuura M, et al. Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine. Gene Ther. 2000;7:1148–1155.
Li S, Huang L . Nonviral gene therapy: promises and challenges. Millenium Review. Gene Ther 2000;7:31–34.
Hernandez A, Zöllner K, Enczmann J, et al. Differential transfection efficiency of the GM-CSF gene into human renal cell carcinoma lines by lipofection. Cancer Gene Ther. 1997;4:59–65.
Boussif O, Gaucheron J, Boulanger C, et al. Enhanced in vitro and in vivo cationic lipid-mediated gene delivery with a fluorinated glycerophosphoethanolamine helper lipid. J Gene Med. 2001;3:109–114.
Audouy S, Molema G, de Leij L, Hoekstra D . Serum as a modulator of lipoplex-mediated gene transfection: dependence of amphiphile, cell type and complex stability. J Gene Med. 2000;2:465–476.
Blackwell JL, Li H, Gomez-Navarro J, et al. Using a tropism-modified adenoviral vector to circumvent inhibitory factors in ascites fluid. Hum Gene Ther. 2000;11:1657–1669.
Brunner S, Sauer T, Carotta S, et al. Cell cycle dependence of gene transfer by lipoplex polyplex and recombinant adenovirus. Gene Therapy 2000;7:401–407.
Acknowledgements
We thank B Hanzen for excellent technical assistance. G R is a member of the Duesseldorf Entrepreneurs Foundation. P D was supported by the Ministry of Science and Research (MSWF), NRW, Germany (Grant 9772125).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Röder, G., Keil, O., Prisack, HB. et al. Novel cGMP liposomal vectors mediate efficient gene transfer. Cancer Gene Ther 10, 312–317 (2003). https://doi.org/10.1038/sj.cgt.7700573
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cgt.7700573
