Common use of Toxicity Clause in Contracts

Toxicity. Although cationic lipids are not immunogenic like viral vectors, they are not without any toxicity. They can be cytotoxic and the extent to which this is manifested differs between different reagents and cell types. The prospect of toxicity is determined by the nature of the cationic carrier as well as the cationic lipid/nucleic acid complex (Lv, H.T. et al., 2006). In terms of cationic lipid/nucleic acid complexes, the toxicity may, in part, be caused by the large size of the complexes, and the high positive zeta potential required for their uptake (Xx, S. et al., 1998, Lv, X.X. xx al., 2006). Therefore the toxicity is also associated with the charge ratio between the cationic lipid species and the nucleic acids, as well as the dose of lipoplexes administered. Higher +/-charge ratios are generally more toxic due to the high positive zeta potential as well as the presence of free (i.e., empty) liposomes (Xx, X. et al., 1999). Free liposomes are present at high charge ratios when lipid is in excess to nucleic acid but their role in transfection efficiency remains unclear. However, Xx et al (1999) showed that their removal did not increase transfection efficiency but did allowed prevention of a decrease in transfection-associated toxicity. Free liposomes may also compete with nucleic acid complexes for interaction with negatively charged membranes and uptake in cells.