Kira Astakhova obtained a PhD degree in bioorganic chemistry in 2009. She continued as a postdoc in the group of Prof. Jesper Wengel at the University of Southern Denmark. In 2012 she became an Associate Professor at the University of Southern Denmark. Until 2015, she was also a visiting professor at the University of California Santa Barbara, Department of Chemistry and Biochemistry, and at Stanford University, USA. She is the author of 35 research publications, 4 book chapters and 2 patents. She was awarded with several research prizes and fellowships including Marie Curie Early Stage Research Training Fellowship and Lundbeck Foundation research prize. Her research interests are interdisciplinary, combining organic chemistry, biomedicine, biophysics and nanobioscience.
The main topic that I will discuss is the synthesis of novel peptide-oligonucleotide conjugates (POCs) and evaluation of their therapeutic potential. Our recent data shows that internally labelled POCs (shown in Chart 1) is a promising class of molecules for specific targeting of DNA and RNA in vitro and in vivo.
There is currently an unmet need for reliable, sequence-specific gene therapeutics that can be efficiently delivered into a target cell. For example, specific gene knock down of a mutated oncogene could become a side effect free treatment of cancer, given that the therapeutic is specifically delivered into tumor cells.
Using synthetic DNA and RNA in the therapy of human diseases is an exciting modern paradigm that is getting a growing attention in the research community. Indeed, synthetic oligonucleotides and their assemblies have much to offer to modern biomedicine. In our recent work we developed new peptide-oligonucleotide conjugates that showed advantageous target recognition properties and stability in human serum for over a week (Taskova et al. Bioconjugate Chem. 2016). As to the delivery issue, it is known that decorating oligonucleotides with peptides such as CPP and NLS, as well as incorporation of fatty acids aid efficient uptake. This implies that in spite of sometimes being challenging, bioconjugation of oligonucleotide opens up exciting opportunities for the new class of therapeutics with previously unachievable activity in vivo.
Our new approach provides an effective practical solution to a problem of developing stable and effective gene therapeutics. Simultaneously, our findings could simplify the development of new gene therapeutics. Other benefits of our research on peptide-oligonucleotide conjugates are chemical advances of the oligonucleotide chemistry and bioconjugation.