Malgorzata Honcharenko
Researcher | Docent
E-mail: malgorzata.honcharenko@ki.se
Visiting address: ,
Postal address: H5 Laboratoriemedicin, H5 BCM El Andaloussi, 141 52 Huddinge
About me
- Malgorzata Honcharenko (Wenska)
-------- Developing methods for delivery of Oligonucleotide conjugates as
therapeutics at ̽»¨¾«Ñ¡ -------------------------------
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
- Article: JOURNAL OF CONTROLLED RELEASE. 2023;357:630-640
- Article: NUCLEIC ACID THERAPEUTICS. 2022;32(3):221-233
- Article: ACS OMEGA. 2021;6(1):579-593
- Article: CURRENT PROTOCOLS IN NUCLEIC ACID CHEMISTRY. 2020;80(1):e102
- Article: BIOCONJUGATE CHEMISTRY. 2019;30(6):1622-1628
- Article: METHODS IN MOLECULAR BIOLOGY. 2019;2036:165-171
- Article: BIOCONJUGATE CHEMISTRY. 2016;27(11):2620-2628
- Article: ORGANIC & BIOMOLECULAR CHEMISTRY. 2016;14(14):3584-3590
- Article: RSC ADVANCES. 2016;6(56):51367-51373
- Article: RSC ADVANCES. 2016;6(10):8326-8337
- Article: CHEMICAL COMMUNICATIONS. 2015;51(99):17552-17555
- Article: BIOORGANIC & MEDICINAL CHEMISTRY. 2013;21(24):7921-7928
- Article: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. 2013;2013(31):7184-7192
- Article: MOLECULES. 2012;17(12):14174-14185
- Article: RSC ADVANCES. 2012;2(33):12949-12962
- Article: NUCLEIC ACIDS RESEARCH. 2011;39(20):9047-9059
- Article: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 2010;132(26):8984-8990
- Article: NUCLEIC ACIDS RESEARCH. 2009;37(9):2867-2881
- Article: NUCLEIC ACIDS RESEARCH. 2009;37(6):1925-1935
- Article: NUCLEIC ACIDS SYMPOSIUM SERIES (2004). 2008;(52):27-28
- Article: NUCLEIC ACIDS SYMPOSIUM SERIES (2004). 2007;(51):149-150
- Article: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 2007;129(26):8362-8379
- Article: HETEROCYCLES. 2007;73(1):303
- Article: ACTA CRYSTALLOGRAPHICA SECTION C: CRYSTAL STRUCTURE COMMUNICATIONS. 2006;62(Pt 7):o405-o409
- Article: ORGANIC & BIOMOLECULAR CHEMISTRY. 2005;3(24):4362-4372
- Article: ORGANIC & BIOMOLECULAR CHEMISTRY. 2002;(1):31-37
- Article: TETRAHEDRON LETTERS. 2001;42(45):8055-8058
- Article: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS. 2000;19(10-12):1487-1503
- Article: TETRAHEDRON LETTERS. 2000;41(13):2227-2229
- Article: ORGANIC & BIOMOLECULAR CHEMISTRY. 1999;(22):3327-3331
- Show more
All other publications
- Conference publication: 2014;:406-407
- Published conference paper: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS. 2003;22(5-8):617-621
- Published conference paper: PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS. 2002;177(6-7):1513-1516
- Published conference paper: ACTA BIOCHIMICA POLONICA. 2001;48(2):429-442
Employments
- Researcher, Department of Laboratory Medicine, ̽»¨¾«Ñ¡, 2022-
Degrees and Education
- Docent, ̽»¨¾«Ñ¡, 2014