Lipoplex-mediated nanovectorization of nucleic acids in gene therapy

Resumo

Gene therapy is a very promising branch of biomedicine that aims to treat inherited or acquired diseases (such as cancer, cardiovascular, neurological and inflammatory diseases) at molecular level. The purpose is to restore correct cell function using nucleic acids (NAs) as therapeutic agents. Depending on the NAs inserted, there are different mechanisms of action. For instance, plasmids DNA (pDNAs) use the patient's biological machinery to replace the defective gene and express the healthy exogenous gene of interest. Other NAs, such as small interfering RNAs (siRNAs), prevent the synthesis of the pathogenic protein by knockdown the corresponding genes. In most cases, NAs require a carrier agent, known as vector, for their internalization into the target cells. Viruses were the source of inspiration during the early stages of gene therapy for the insertion of NAs into cells. Nowadays, viral vectors are still in use due to their high efficiency; however, the undesirable adverse effects associated with their use are forcing the search for alternatives. Among the different synthetic options for non-viral vectors, polymeric and colloidal systems stand out. Within colloidal systems, cationic lipids (CLs) are perhaps the most studied group due to their ability to interact electrostatically with anionic NAs, and spontaneously self-organize in aqueous solution forming structures similar to that of the cell membrane. The resulting complex between the CLs and NAs, well-known as lipoplex, must transport the NAs into cells and release them into the cytoplam without causing damage. The efficiency of this process will depend on the vector’s capacity to overcome the known biological barriers during its physiological journey...