KLN-5: A safe monocationic lipophosphoramide to transfect efficiently haematopoietic cell lines and human CD34 + cells
Résumé
The safe and efficient delivery of nucleic acids into haematopoietic stem cells (HSCs) has a wide range of therapeutic applications. Although viruses are being used in most clinical trials owing to their high transfection efficacy, recent results highlight many concerns about their use. Synthetic transfection reagents, in contrast, have the advantage of being safe and easy to manage while their low transfection efficiency remains a hurdle that needs to be addressed before they can be widely used. Using information on transfection mechanisms, a new family of monocationic lipids called lipophosphoramides was synthesized. Their efficiency to transfer genes into haematopoietic cell lines (K562, Jurkat and Daudi) and CD34 + cells was assessed. In this study, we report that one of these new compounds, KLN-5, leads to more efficient transfection activity than one of our previously most efficient reagents (EG-308) and the commercially available monocationic lipids (DC-CHOL and DOTAP/DOPE) (P<0.05). In addition, only a slight toxicity related to the chemical structure of the new compounds is observed. Moreover, we show that KLN-5 can successfully carry the transgene into haematopoietic progenitor cells (CD34 +). These results demonstrate that synthetic transfection reagents represent a viable alternative to viruses and could have potential practical utility in a number of applications. © 2004 Elsevier B.V. All rights reserved.
Mots clés
CD34 antigen
monocationic lipophosphoramide
phosphoramidic acid derivative
unclassified drug
article
controlled study
genetic transfection
hematopoietic cell
human
human cell
priority journal
safety
stem cell
toxicity
transgene
Amides
Antigens
CD34
beta-Galactosidase
Blood Cells
Cell Line
Tumor
Cholesterol
Fatty Acids
Monounsaturated
Hematopoietic Stem Cells
Humans
Lipids
Organophosphorus Compounds
Phosphatidylethanolamines
Phosphoric Acids
Plasmids
Quaternary Ammonium Compounds
Structure-Activity Relationship
Transfection