Malgorzata Honcharenko

Researcher | Docent
Visiting address: ,
Postal address: H5 Laboratoriemedicin, H5 BCM El Andaloussi, 141 52 Huddinge
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About me

  • Malgorzata Honcharenko (Wenska)
    -------- Developing methods for delivery of Oligonucleotide conjugates as
    therapeutics at Karolinska Institutet -------------------------------

Research

  • Developing new methods for improving action of therapeutic modalities like
    oligonucleotides, peptides and bioconjugates is a fundament of my research at
    KI. I examine a range of scientific tools with the aim to improve targeting
    therapeutics to precise destination in the body, contributing to the
    discoveries of the future precise therapies. Many therapeutic approaches can
    be improved and unwanted side effects avoided. We should design therapeutics
    in such a way that they will be delivered and released precisely to the
    affected organ/tissue in the body (targeted delivery approach).
    As a part of European network I am applying developed at KI methods for
    improvements of oligonucleotide based therapies (e.g. COST Action: Delivery
    of Antisense RNA Therapeutics). As a bioconjugation chemist I seek
    interdisciplinary collaborations with medicinal, biological and biochemical
    experts to explore the potential of the methods I developed to improve
    therapies. Some of the key collaborators include: Prof. Aartsma-Rus at the
    Leiden University Medical Center (LUMC), The Netherlands, and Shalini
    Andersson Chief Scientist New Therapeutic Modalities at AstraZeneca,
    Gothenburg.
    After working on several projects developing more effective therapeutics I
    recognize the importance of finding solution to the general problem of their
    precise delivery. Methods that I developed at KI allows for efficient
    conjugation of receptor specific entities to oligonucleotides. That improves
    delivery of those molecules to the place of action. However, ligand-receptor
    interaction is usually weak, and current methods allow for conjugations of
    just several such ligands to oligonucleotide. On the other hand, exosomes
    that are 30-200 nm in diameter, can be equipped with several hundreds of
    copies (~ 600, depending of the EVs size) magnifying the targeting effect.
    This is the reason why bio-engineered EVs may be just the answer that
    scientists are looking for in targeted drug delivery and a main collaborative
    project at the moment.
    15 Selected Publications
    (1) Smith, E., Moreno, P.,
    Stroemberg, R., and Wenska, M. (2015). Patent, US 9067964 B2 20150630
    (2) Honcharenko, M., Honcharenko,
    D., and Strömberg, R. (2019) Attachment of Peptides to Oligonucleotides on
    Solid Support Using Copper(I)-Catalyzed Huisgen 1, 3-Dipolar Cycloaddition.
    Oligonucleotide-Based Therapies: Methods and Protocols, Methods in Molecular
    Biology vol. 2036.
    (3) Honcharenko, M., Honcharenko,
    D., and Stroemberg, R. (2019) Efficient Conjugation to Phosphorothioate
    Oligonucleotides by Cu-Catalyzed Huisgen 1, 3-Dipolar Cycloaddition.
    Bioconjugate Chem. 30, 1622-1628.
    (4) Gissberg, O. I., Jezowska,
    M., Zaghloul, E. M., Bungsu, N. I., Stroemberg, R., Smith, C. I. E., Lundin,
    K. E., and Honcharenko, M. (2016) Fast and efficient synthesis of Zorro-LNA
    type 3'-5'-5'-3' oligonucleotide conjugates via parallel in situ stepwise
    conjugation. Org. Biomol. Chem. 14, 3584-3590.
    (5) Honcharenko, M., Bestas, B.,
    Jezowska, M., Wojtczak, B. A., Moreno, P. M. D., Romanowska, J., Baechle, S.
    M., Darzynkiewicz, E., Jemielity, J., Smith, C. I. E., and Stroemberg, R.
    (2016) Synthetic m3G-CAP attachment necessitates a minimum trinucleotide
    constituent to be recognised as a nuclear import signal. RSC Adv. 6,
    51367-51373.
    (6) Jezowska, M., Honcharenko,
    D., Ghidini, A., Stroemberg, R., and Honcharenko, M. (2016) Enabling Multiple
    Conjugation to Oligonucleotides Using "Click Cycles". Bioconjugate Chem. 27,
    2620-2628.
    (7) Wojtczak, B. A., Warminski,
    M., Kowalska, J., Lukaszewicz, M., Honcharenko, M., Smith, C. I. E.,
    Stromberg, R., Darzynkiewicz, E., and Jemielity, J. (2016) Clickable
    trimethylguanosine cap analogs modified within the triphosphate bridge:
    synthesis, conjugation to RNA and susceptibility to degradation. RSC Adv. 6,
    8317-8328.
    (8) Ruiz Garcia, Y., Iyer, A.,
    Van Lysebetten, D., Vladimir Pabon, Y., Louage, B., Honcharenko, M., De
    Geest, B. G., Edvard Smith, C. I., Stromberg, R., and Madder, A. (2015)
    Sequence-selective DNA recognition and enhanced cellular up-take by
    peptide-steroid conjugates. Chem. Commun. (Cambridge, U. K.) 51, 17552-17555.
    (9) Honcharenko, M., Zytek, M.,
    Bestas, B., Moreno, P., Jemielity, J., Darzynkiewicz, E., Smith, C. I. E.,
    and Stroemberg, R. (2013) Synthesis and evaluation of stability of m3G-CAP
    analogues in serum-supplemented medium and cytosolic extract. Bioorg. Med.
    Chem. 21, 7921-7928.
    (10) Honcharenko, M., Romanowska, J.,
    Alvira, M., Jezowska, M., Kjellgren, M., Edvard Smith, C. I., and Stroemberg,
    R. (2012) Capping of oligonucleotides with "clickable" m3G-CAPs. RSC Adv. 2,
    12949-12962.
    (11) Jezowska, M., Romanowska, J.,
    Bestas, B., Tedebark, U., and Honcharenko, M. (2012) Synthesis of biotin
    linkers with the activated triple bond donor [p-(N-propynoylamino)toluic
    acid] (PATA) for efficient biotinylation of peptides and oligonucleotides.
    Molecules 17, 14174-14185.
    (12) Wenska, M., Alvira, M.,
    Steunenberg, P., Stenberg, A., Murtola, M., and Stroemberg, R. (2011) An
    activated triple bond linker enables "click" attachment of peptides to
    oligonucleotides on solid support. Nucleic Acids Res. 39, 9047-9059.
    (13) Murtola, M., Wenska, M., and
    Stroemberg, R. (2010) PNAzymes That Are Artificial RNA Restriction Enzymes.
    J. Am. Chem. Soc. 132, 8984-8990.
    (14) Bramsen, J. B., Laursen, M. B.,
    Nielsen, A. F., Hansen, T. B., Bus, C., Langkjaer, N., Babu, B. R., Hojland,
    T., Abramov, M., Van Aerschot, A., Odadzic, D., Smicius, R., Haas, J.,
    Andree, C., Barman, J., Wenska, M., Srivastava, P., Zhou, C., Honcharenko,
    D., Hess, S., Mueller, E., Bobkov, G. V., Mikhailov, S. N., Fava, E., Meyer,
    T. F., Chattopadhyaya, J., Zerial, M., Engels, J. W., Herdewijn, P., Wengel,
    J., and Kjems, J. (2009) A large-scale chemical modification screen
    identifies design rules to generate siRNAs with high activity, high stability
    and low toxicity. Nucleic Acids Res. 37, 2867-2881.
    (15) Moreno, P. M. D., Wenska, M.,
    Lundin, K. E., Wrange, O., Stroemberg, R., and Smith, C. I. E. (2009) A
    synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and
    nucleic acids. Nucleic Acids Res. 37, 1925-1935.

Articles

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Employments

  • Researcher, Department of Laboratory Medicine, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2014

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