Designer gene transfer tools (vectors) are key in treating different inherited or acquired diseases safely with gene therapy. With the help of multilevel-optimized vectors based on the Human Immunodeficiency Virus 1 (HIV-1) and CRISPR/Cas, we pursue to develop an effective and safe gene therapy treatment to familial hypercholesterolemia and heart failure, both important diseases in Finland but also leading causes of deaths worldwide. Our research also includes the creation of safe and optimally efficient CAR T cells for cell therapy of cancer, studying the role of nucleoli in health and disease, characterizing genome-wide effects of transgene integration, and assessing the safety of gene transfer. We have shown that the natural tendency lentivirus vectors (LVs) to integrate in a nearly random manner can be modified so that they are less likely to destroy important cellular genes or cause other unwanted side-effects. The modified vectors can also be harnessed for the delivery of desired proteins into target cells. Our approaches to improve the safety and efficiency of gene therapy treatments include multi-level targeting of LVs to the cells and tissues most relevant to achieve a curative outcome and through minimizing the risks for undesired side effects, including insertional mutagenesis and immunogenicity.
I am part of the The GeneCellNano consortium funded by the Academy of Finland’s Flagship Programme.
Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
+358 40 355 3812
Research groups and research projects
RESEARCH GROUPS - UEF
Schenkwein, Diana; Afzal, Saira; Nousiainen, Alisa; Schmidt, Manfred; Ylä-Herttuala, Seppo. 2020. Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus Molecular therapy 28 8: 1-18. 2020
Schenkwein, Diana; Ylä-Herttuala, Seppo. 2018. Gene Editing of Human Embryos with CRISPR/Cas9: Great Promise Coupled with Important Caveats Molecular therapy 26 3: 659-660. 2018
Schenkwein D, Ylä-Herttuala S. 2016. Development of lentiviral vectors for targeted integration and protein delivery. In: Maurizio Federico (ed.) Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools. Springer science+business media. Methods in Molecular Biology 1448, Part III. s. 185-198. 2016
Dijkstra MH, Pirinen E, Huusko J, Kivelä R, Schenkwein D, Alitalo K, Ylä-Herttuala S. 2014. Lack of cardiac and high-fat diet induced metabolic phenotypes in two independent strains of Vegf-b knockout mice. Scientific Reports 4, Article number:6238: --. 2014
Turkki Vesa, Schenkwein Diana, Timonen Oskari, Husso Tiia, Lesch Hanna P, Ylä-Herttuala Seppo. 2014. Lentiviral protein transduction with genome-modifying HIV-1 integrase-I-PpoI fusion proteins: studies on specificity and cytotoxicity. BioMed research international 2014;2014:379340.: Article ID 379340. 2014
Schenkwein, Diana. 2013. An improved lentivirus vector for safer transgene integration and protein transduction. Itä-Suomen yliopisto. Publications of the University of Eastern Finland. Dissertations in Health Sciences 164. 2013
Schenkwein D, Turkki V, Ahlroth MK, Timonen O, Airenne KJ, Ylä-Herttuala S. 2012. rDNA-directed integration by an HIV-1 integrase--I-PpoI fusion protein. NUCLEIC ACIDS RESEARCH 2012 Dec 28. [Epub ahead of print]: --. 2012
Schenkwein D, Turkki V, Kärkkäinen HR, Airenne K & Ylä-Herttuala S. 2010. Production of HIV-1 integrase fusion protein-carrying lentiviral vectors for gene therapy and protein transduction. HUMAN GENE THERAPY 21: 589-602. 2010
Samaranayake H, Wirth T, Schenkwein D, Räty JK, Ylä-Herttuala S. 2009. Challenges in monoclonal antibody-based therapies. Annals of Medicine 41 5: 322-331. 2009
Laitinen OH, Airenne KJ, Hytönen VP, Peltomaa E, Mähönen AJ, Wirth T, Lind MM, Mäkelä KA, Toivanen PI, Schenkwein D, Heikura T, Nordlund HR, Kulomaa MS, Ylä-Herttuala S. 2005. A multipurpose vector system for the screening of libraries in bacteria, insect and mammalian cells and expression in vivo. NUCLEIC ACIDS RESEARCH 33 4: e42. 2005