On 14 September at 9:15 Krista Freimann will defend her doctoral thesis „Design of peptide-based vector for nucleic acid delivery in vivo“.
Professor, PhD Ülo Langel
Senior Research Fellow, PhD Kaido Kurrikoff
PhD Angelita Rebollo Garcia, Inserm, France (Directeur de Recherche, Inserm, France. Senior scientist at CSIC, Espagne, permanent positions)
Various serious genetic diseases, such as cystic fibrosis, Duchenne muscular dystrophy and cancer can be treated with gene therapy. Gene therapy can be utilized to regulate the expression of disease causing genes by using therapeutic nucleic acids. Due to their size and cationic nature, these nucleic acids need vectors to enhance their delivery into the diseased tissue. Although impressive results have been accomplished with virus-derived gene delivery vectors their utilization is not without risks and increasingly more effort has been applied into the research of non-viral vectors. Cell penetrating peptides are one group of non-viral delivery vectors. Cell penetrating peptides (CPP) are short cationic and/or amphipathic peptides than are shown to significantly improve the delivery of various biomolecules in vitro and in vivo. The main hindrances of using CPPs are the lack of transfection efficacy and selectivity in vivo. In addition, the size and heterogenous size distribution of prepared CPP-DNA particles also alters the bio-distribution of particles and can cause side-effects.
In this thesis we aimed to tackle these previously mentioned main problems of utilization of CPPs. We designed a novel effective CPP NF55 for the systemic delivery of DNA. Thereafter we developed a novel method to prepare stable and uniformly sized particles for systemic gene delivery in vivo. Subsequently, we used incorporation of magnetic iron oxide particles to further increase the efficacy and specificity of the peptide vectors. Taken together, we designed more efficient and safer formulations of CPP/nucleic acid particles for the systemic in vivo delivery of nucleic acids.