Aspects of nonviral gene therapy: Correlation of molecular parameters with lipoplex structure and transfection efficacy in pyridinium-based cationic lipids

Efficient and non-toxic gene delivery by anionic lipoplexes based on polyprenyl ammonium salts and their effects on cell physiology

“…Furthermore, the multitude of pathways and mechanisms implicated in the process of lipofection accounts for the complexity of the structure–safety–efficiency relationships . Conflicting reports on the effect of vectors and lipoplex properties on transfection efficiency additionally hinder the application of new lipids and co‐lipids in gene delivery . Therefore, trials on the improvement of the lipofection strategy are still largely based on empirical approaches towards the formulation of optimal lipids, especially in the case of new and distinct classes of lipofecting compounds.…”

Self-assembling systems based on diquaternized derivatives of 1,4-diazabicyclo[2.2.2]octane

“…[1][2][3][4]. Therefore, the design of novel cationic surfactants with advanced characteristics is in the focus of modern technologies.…”

Ligand-Tagged Cationic Liposome Facilitates Efficient Gene Delivery to Folate Receptors

“…Synthetic lipids, due to their low toxicity, relative ease of large-scale production and purification, coupled with their ability to exist in many self-assembled macromolecular shapes under varying conditions of formulation provide a versatile material for lipofection. Majority of synthetic non-viral lipids for transfection contain a positively charged head group, typically tertiary or quaternary ammonium groups or polyamines, and a hydrophobic domain based on either alkyl chains or cholesterol and a spacer 4 . Excessive positive charges on vectors can ultimately undermine the transfection efficiency.…”

“…Protection (from serum nucleases) and cellular delivery of the genetic cargo are achieved by packaging the integrally negatively charged nucleic acid with the cationic liposomes into a compacted particle (a lipoplex), driven by electrostatic and hydrophobic interactions 6,7 . The success of the gene transfer vectors, characterized by a heterocyclic polar head group, has been attributed in large measure to the delocalized positive charge which offers a favourable electrostatic interaction 8 . This diffuse charge offers precisely an appropriate balance between binding the nucleic acid cargo and subsequent cargo release through endosomal escape 8 .…”

“…The success of the gene transfer vectors, characterized by a heterocyclic polar head group, has been attributed in large measure to the delocalized positive charge which offers a favourable electrostatic interaction 8 . This diffuse charge offers precisely an appropriate balance between binding the nucleic acid cargo and subsequent cargo release through endosomal escape 8 . Strategies to improve the efficiency and biocompatibility of cationic elements for gene delivery typically involve grafting the functional ligands, such as lipids, peptides and sugars or a combination thereof, to advance the stability, targeting, uptake and sub-cellular trafficking capabilities of the carrier 9 .…”