Structure and kinetics of synthetic, lipid-based nucleic acid carriers

Autor: Nily Dan
Rok vydání: 2018
Předmět:
DOI: 10.1016/b978-0-12-813687-4.00014-1
Popis: Nucleic acid–based therapies use DNA or siRNA to treat genetic disorders caused by gene abnormality, such as hemoglobinopathies (sickle cell disease, beta-thalassemia), cystic fibrosis, or some types of cancer. Complexes between nucleic acids and cationic phospholipids, lipoplexes, are a promising, synthetic gene carrier for both in vitro and in vivo applications. However, optimization of the complex performance requires better understanding and control of lipoplex properties. Lipoplex structure is characterized on two lengths. On the local scale, namely, 10–50 nm, the lipid and nucleic acid arrangement is set by thermodynamic equilibrium and is directly linked to the molecular properties of the lipids and concentration of nucleic acid. On larger scales, in the order 100 nm–1 μm, lipoplex characteristics are set by the kinetics of the synthesis process, following a three-step process: (1) an initial stage (on timescales of less than 1 min) where the nucleic acid adsorbs onto the lipid assembly; (2) a growth stage, where complexes flocculate, characterized by a broad range of timescales from minutes to hours, depending on system parameters; and (3) internal equilibration stage where the outer lipoplex structure remains constant, which may take hours or more.
Databáze: OpenAIRE