Diana Schenkwein
Yliopistotutkija
A.I. Virtanen -instituutti, Terveystieteiden tiedekunta
diana.schenkwein@uef.fi
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.
Tutkimusryhmät
Projektit
Julkaisut
11/11 kappaletta-
Characterization of a new IN-I-PpoI fusion protein and a homology-arm containing transgene cassette that improve transgene expression persistence and 28S rRNA gene-targeted insertion of lentiviral vectors
Nousiainen, Alisa; Schenkwein, Diana; Ylä-Herttuala, Seppo. 2023. PLoS ONE. 18: -
Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus
Schenkwein, Diana; Afzal, Saira; Nousiainen, Alisa; Schmidt, Manfred; Ylä-Herttuala, Seppo. 2020. Molecular therapy. 28: 1-18 -
Gene Editing of Human Embryos with CRISPR/Cas9: Great Promise Coupled with Important Caveats
Schenkwein, Diana; Ylä-Herttuala, Seppo. 2018. Molecular therapy. 26: 659-660 -
Development of lentiviral vectors for targeted integration and protein delivery
Schenkwein D, Ylä-Herttuala S. Teoksessa: Maurizio Federico(toim.) , 2016. Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools. s. 185-198. Springer Science+Business Media -
Lack of cardiac and high-fat diet induced metabolic phenotypes in two independent strains of Vegf-b knockout mice
Dijkstra MH, Pirinen E, Huusko J, Kivelä R, Schenkwein D, Alitalo K, Ylä-Herttuala S. 2014. Scientific reports. 4, Article number:6238: -- -
Lentiviral protein transduction with genome-modifying HIV-1 integrase-I-PpoI fusion proteins: studies on specificity and cytotoxicity
Turkki Vesa, Schenkwein Diana, Timonen Oskari, Husso Tiia, Lesch Hanna P, Ylä-Herttuala Seppo. 2014. Biomed research international. 2014;2014:379340.: Article ID 379340 -
An improved lentivirus vector for safer transgene integration and protein transduction
Schenkwein, Diana. 2013. Publications of the University of Eastern Finland. Dissertations in Health Sciences -
rDNA-directed integration by an HIV-1 integrase--I-PpoI fusion protein
Schenkwein D, Turkki V, Ahlroth MK, Timonen O, Airenne KJ, Ylä-Herttuala S. 2012. Nucleic acids research. : -- -
Production of HIV-1 integrase fusion protein-carrying lentiviral vectors for gene therapy and protein transduction
Schenkwein D, Turkki V, Kärkkäinen HR, Airenne K & Ylä-Herttuala S. 2010. Human gene therapy. 21: 589-602 -
Challenges in monoclonal antibody-based therapies
Samaranayake H, Wirth T, Schenkwein D, Räty JK, Ylä-Herttuala S. 2009. Annals of medicine. 41: 322-331