EVs are vesicles produced by all cells for intercellular communication. They can be loaded with macro molecular cargo such as CRISPR-Cas, shRNA, or siRNA for delivery to recipient cells, in vitro as well as in vivo. These macromolecules can be designed specifically to treat any given disease, however, the issue with macro molecular drugs is delivery to the correct target cells in adequate concentrations. Therefore, we aim to use advanced genetic screening methods to develop novel targeting tools for the delivery of macromolecules by EVs as well as local production of loaded EVs by engineered cells.
To increase the local concentration of therapeutic EVs we work with two main projects:
Local production of engineered EVs by genetically modified cells
In this project we aim to modify cells to be activated by specific antigens in the diseased microenvironment, where the activation triggers the production of engineered EVs. This leads to a locally high but systemically low concentrations of therapeutic EVs. At first, this technique will be used to treat pancreatic cancer, which is a cancer type with very poor prognosis.
Novel methods to improve EV targeting
In this project, several novel methods will be evaluated to increase the targeting of EVs to different organs and specific cell populations within an organ. Presently, the targeting capability of nanoparticles is rather inefficient with only a minor percentage of the injected dose reaching the diseased organ or tumor. Within this project, we will use synthetic biology and proteins inspired by viruses to enhance the targeting of EVs to specific cell populations in vivo. The aim is to specifically deliver loaded cargo to hematopoietic stem cells to treat inherited diseases affecting the immune system and healthy blood formation.
Ambitious students who are interested in carrying out their master’s degree project in a student-friendly environment are welcome to contact us for more information.
Vetenskapsrådet, Evox Therapeutics, CIMED.
Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles.
Gupta D, Wiklander OPB, Görgens A, Conceição M, Corso G, Liang X, Seow Y, Balusu S, Feldin U, Bostancioglu B, Jawad R, Mamand DR, Lee YXF, Hean J, Mäger I, Roberts TC, Gustafsson M, Mohammad DK, Sork H, Backlund A, Lundin P, de Fougerolles A, Smith CIE, Wood MJA, Vandenbroucke RE, Nordin JZ, El-Andaloussi S
Nat Biomed Eng 2021 09;5(9):1084-1098
Efficient Peptide-Mediated In Vitro Delivery of Cas9 RNP.
Gustafsson O, Rädler J, Roudi S, Lehto T, Hällbrink M, Lehto T, Gupta D, Andaloussi SE, Nordin JZ
Pharmaceutics 2021 Jun;13(6):
Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging.
Gupta D, Liang X, Pavlova S, Wiklander OPB, Corso G, Zhao Y, Saher O, Bost J, Zickler AM, Piffko A, Maire CL, Ricklefs FL, Gustafsson O, Llorente VC, Gustafsson MO, Bostancioglu RB, Mamand DR, Hagey DW, Görgens A, Nordin JZ, El Andaloussi S
J Extracell Vesicles 2020 Aug;9(1):1800222
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides.
Nordin JZ, Mizobe Y, Nakamura H, Komaki H, Takeda S, Aoki Y
J Vis Exp 2020 05;(159):
Tangential Flow Filtration with or Without Subsequent Bind-Elute Size Exclusion Chromatography for Purification of Extracellular Vesicles.
Nordin JZ, Bostancioglu RB, Corso G, El Andaloussi S
Methods Mol Biol 2019 ;1953():287-299