Transfection activity relationships

Cationic Lipids Molecular Structure/ Transfection Activity Relationships and Interactions with Biomembranes... 

Cationic Lipids Molecular Structure/Transfection Activity Relationships... 

Koynova R, Tenchov B (2009) Cationic phospholipids - structure/transfection activity relationships. Soft Matter 5 3187-3200... 

The transfection mechanism of plasmid-chitosan complexes as well as the relationship between transfection activity and cell uptake was analyzed by using fluorescein isothiocyanate-labeled plasmid and Texas-Red-labeled chitosan. Several factors affect transfection activity and cell uptake, for example the molecular mass of chitosan, stoichiometry of complex, seriun concentration and the pH of the transfection medium. The level of transfection with plasmid-chitosan complexes was found to be highest when the molecular mass of chitosan was 40 or 84 kDa, the ratio of chitosan nitrogen to DNA phosphate was 5, and serum at pH 7.0 was 10%. Plasmid-chitosan complexes most likely condense to form large aggregates (5-8 p,m), which absorb to the cell surface. After this, plasmid-chitosan complexes are endocytosed, and accumulate in the nucleus [97]. 

Urotensin II Receptor (GPR14). The vasoactive cyclic peptide urotensin II (U-II) is the endogenous ligand of the G protein-coupled orphan receptor GPR14. Structure-activity relationships from 25 peptide analogs, which mobilize intracellular calcium in GPR14-transfected CHO cells, and the... 

Unlike DOGSDSO, the present series harbor disulfide bonds in every important position of the cationic lipid. Similarly to RPR120535, these cationic hpids are not formulated with DOPE or other co-lipid(s) for optimal transfection efficiency. Based on exhaustive structure-activity relationship studies, we concluded that RPR-132688 is ten times more active than RPR120535. 

Niculescu-Duvaz D, Heyes J, Springer CJ (2003) Structure-activity relationship in cationic lipid mediated gene transfection. Curr Med Chem 10 1233-1261... 

Soltan MK, Ghonaim HM, El Sadek M et al (2009) Design and synthesis of N-4, N-9-disubstituted spermines for non-viral siRNA delivery - structure-activity relationship studies of transfection efficiency versus toxicity. Pharm Res 26 286-295... 

Chemical programming of polymers has proven to be a crucial tool in mimicking virus-like features. Thus, alterations in polymer structure and conformation can be correlated to transfection efficiency and cytotoxicity. It has to be considered that the better polymer structure is defined, the more detailed study of structure-activity relationships is possible. First approaches towards better defined polymer structure with narrow molecular weight distribution have been made by PAE and pseudo-dendrimer synthesis already discussed in Sect. 4.1. 

A summary and discussion of empirical data on relationships between cationic lipid molecular structure and transfection activity are provided by Koynova and Tenchov Structural features of cationic lipids are related to their interaction with biomembranes and the uptake efficiency of transfection complexes. 

Inside-out vesicles can be perfectly used to study single efflux processes, because preloading of cells is not necessary and because of well-defined study conditions with transporter directly facing compound concentration in the incubation medium in contrast to double-transfected cell lines (3.1.2.4.L). Therefore, these studies allow establishing structure activity relationships (SAR) for one efflux transporter only. 

---