Browsing by Author "Kopilow, Alisa"

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  • Immune response of surface modified DNA nanostructures
    (2017-10-23) Kopilow, Alisa
     Kemian tekniikan korkeakoulu | Master's thesis
    DNA nanotechnology has seen remarkable growth during the past decade. The exceptionally predictable self-assembly of DNA makes it an ingenious building block. Especially after the establishment of DNA origami, a vast array of DNA nanoapplications have emerged spanning multiple fields from nanoelectronics to biomimetic applications. DNA origami-based nanostructures have shown particularly great promise in biomedical applications. However, these applications still suffer from low stability in biological environments, and poor transfection rates. Additionally, biocompatibility is crucial. Although DNA is inherently biocompatible, any foreign DNA is seen as a threat and typically induces an immune response. This immune activation can result in treatment failure or significant side-effects. In this work, two kinds of surface-modifications are applied on a model DNA origami structure in order to achieve improved stability, reduce the immunogenic effect of bare DNA, as well as to synthesize functional nanostructures. The achieved structures were characterized with electrophoretic mobility shift assays, transmission electron microscopy and ultraviolet-visible spectroscopy. The immunogenicity was assessed by measuring the IL-6 secretion induced in primary murine splenocytes. First, DNA origami structures were surface-modified with bovine serum albumin, which has been used to reduce unwanted immune response. As anticipated, the BSA-G2 protein-dendron coating successfully attenuated the immunogenic effect of bare DNA origami. Additionally, DNA origami was utilized to create ordered phthalocyanine structures, in order to achieve enhanced optical properties by reducing the aggregation tendencies of phthalocyanines. These DNA complexes could potentially be utilized to produce functional nanostructures for imaging, therapeutic applications and drug delivery.
  • Polyisobuteenit lääketieteellisinä biomateriaaleina
    (2014-12-28) Kopilow, Alisa
     Sähkötekniikan korkeakoulu | Bachelor's thesis
  • Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility
    (2017-09) Auvinen, Henni; Zhang, Hongbo; Nonappa, Nonappa; Kopilow, Alisa; Niemelä, Elina H.; Nummelin, Sami; Correia, Alexandra Mr; Santos, Hélder A.; Linko, Veikko; Kostiainen, Mauri A.
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Fully addressable DNA nanostructures, especially DNA origami, possess huge potential to serve as inherently biocompatible and versatile molecular platforms. However, their use as delivery vehicles in therapeutics is compromised by their low stability and poor transfection rates. This study shows that DNA origami can be coated by precisely defined one-to-one protein-dendron conjugates to tackle the aforementioned issues. The dendron part of the conjugate serves as a cationic binding domain that attaches to the negatively charged DNA origami surface via electrostatic interactions. The protein is attached to dendron through cysteine-maleimide bond, making the modular approach highly versatile. This work demonstrates the coating using two different proteins: bovine serum albumin (BSA) and class II hydrophobin (HFBI). The results reveal that BSA-coating significantly improves the origami stability against endonucleases (DNase I) and enhances the transfection into human embryonic kidney (HEK293) cells. Importantly,it is observed that BSA-coating attenuates the activation of immune response in mouse primary splenocytes. Serum albumin is the most abundant protein in the blood with a long circulation half-life and has already found clinically approved applications in drug delivery. It is therefore envisioned that the proposed system can open up further opportunities to tune the properties of DNA nanostructures in biological environment, and enable their use in various delivery applications.
  • Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility
    (2017) Auvinen, Henni; Zhang, Hongbo; Nonappa, Nonappa; Kopilow, Alisa; Niemelä, Elina H.; Nummelin, Sami; Correia, Alexandra; Santos, Hélder A.; Linko, Veikko; Kostiainen, Mauri A.
     School of Science | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä