Kombinationsmolekyler för genterapi : Konjugat mellan peptider och oligonukleotider

Sammanfattning: The report examines how the market, as well as purification conditions, forpeptide-oligonucleotide conjugates look like today. These conjugates are intended to be usedin drugs to treat otherwise incurable diseases but so far these types of molecules are still intest-phases and no finished conjugate is on the market yet. However, the drug SRP-5051 is inclinical phase II and it is expected to be seen on the market no earlier than May 2022. Thedrug consists of a phosphorodiamidate morpholino oligomer conjugated to a cationiccell-penetrating peptide. The aim of the project was to gain an understanding of what currentresearch looks like, what types of conjugates seem to be the most promising and whatchallenges there are with these. In addition, various purification possibilities for the mostpromising conjugates were also investigated. The report is a literature study and containsinterviews with experts in the field. The oligonucleotide most likely to occur in a futureconjugate consists of a charge-neutral phosphorodiamidate morpholino oligomer (PMO) orpeptide nucleic acid (PNA), which are spinal modifications that increase stability and affinity.The peptide in such a conjugate needs to perform endocytosis and is therefore expected to becationic. The amount of arginine in the peptide is correlated with both efficiency and toxicity,which is the major challenge of the conjugates today. The purification is performed with acation exchanger where the cationic charge of the peptide is utilized. Elution takes place witha salt gradient, if necessary a secondary purification step in the form of size exclusion is used.