Ly Pärnaste will defend her doctoral thesis titled „How, why, what and where: Mechanisms behind CPP/cargo nanocomplexes“ on 17 June at 10:15.
Supervisors: professor Ülo Langel (Tartu Ülikool), teadur Piret Arukuusk (Tartu Ülikool)
Opponent: professor Fernando Albericio, PhD. University of Barcelona, Spain; University of KwaZulu-Natal, Durban, South Africa.
Summary: Many diseases are caused by defects in genetic information of a living organism. One approach to alleviate the disease state or cure it permanently is the use of gene therapy. Gene therapy is the harnessing of nucleic acid (NA) molecules to alter gene expression or express a gene lacking in the cell. In gene therapy, the limited delivery of therapeutic NAs is the major obstacle curbing their use in medicine. The clinical use of NAs is restricted due to their low uptake into cells, because of their high molecular weight, negative charge, hydrophilic nature and lack of efficient uptake pathway for NAs. In addition to these, NAs are prone to enzymatic degradation by enzymes in the serum, extracellular matrix and in the cells. In order to increase the NAs use for therapeutic and biotechnological approaches, several methods have been developed. Viral vectors are considered the most efficient type of delivery method, but there are several concerns connected to innate properties of viruses, that have led to the development of physical and chemical approaches for delivery. One of highly potential approaches is the use of cell-penetrating peptides (CPPs) - a class of chemical vectors, that are able to cross cell membranes and carry into the cell different types of cargoes, including NAs. CPPs are short amino acid sequences that usually contain positively charged amino acids in their sequence. When CPPs are mixed with NAs, they are able to form non-covalently associated nanoparticles. The physico-chemical properties of CPP/NA nanoparticles and how these are linked to interactions with cells, intracellular trafficking and final biological effect gained from delivered cargo is an important field of study that could give us the basis for further development of chemical delivery vectors. These vectors could be used for biotechnological approaches, such as protein production in cultured cells, and gene therapy approaches.