Research group - Samir EL Andaloussi
Our research efforts focus on one of the greatest challenges facing modern therapeutics; delivery. Despite the unprecedented knowledge of diseases and their mechanisms due to advances in biomedical sciences; many promising therapeutic approaches are still clinically unavailable. This is simply because there is no efficient means of delivering these therapeutics to the right organ with the right dose.
Such therapeutics include proteins for replacement therapy or antibodies for anti-inflammatory treatment as well as nucleic acids for gene therapy of diseases including muscular dystrophies and neurodegenerative disorders. We develop innovative drug delivery technologies that are able to carry protein and/or gene therapies to the target tissues safely and efficiently. We have developed a promising technology based on reprogramming exosomes, which are vesicles that are naturally used by cells to communicate, to carry therapeutic proteins and nucleic acids. We engineer exosomes with enhanced delivery and targeting capacities and screen our wide array of exosome designs in disease-relevant cellular and animal models. We are also developing methods for large-scale production and purification of such exosome therapeutics. Additionally, our lab develops methods for gene therapy based on modified cell-penetrating peptides that are efficient carriers of nucleic acids and proteins across biological barriers. We test our different technologies in models of inflammatory diseases as well as neurodegenerative and neuromuscular disorders. Our main aim is to one day unlock the potential of protein and gene therapy of such diseases by the development of novel and efficient delivery technologies.
In the ERC Consolidator project DELIVER, we propose a platform development using synthetic nanocarriers to transiently engineer hepatic cells in vivo and harness extracellular vesicles to functionally deliver drugs to unreachable organs, focusing on the brain. Genetic constructs will be developed that allow for transient in situ engineering of cells in vivo and release of cargo-laden extracellular vesicles for further delivery. The same strategy will be exploited using nanoparticles injected locally in brain to secrete extracellular vesicles loaded with the disease-relevant proteins as a treatment strategy for Parkinson’s disease. Long-term this novel project has enormous potential, as any engineered extracellular vesicles could be produced in situ.
Research group leader - Samir EL Andaloussi
Swedish Medical Research Council, SSF-IRC FormulaEx, H2020 EXPERT, KI central faculty funding, Swedish Society of Medical Research, Vinnova, ONO Pharma, KID funding, EvoxTherapeutics, US Army.
Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle.
Conceição M, Forcina L, Wiklander OPB, Gupta D, Nordin JZ, Vrellaku B, et al
Biomaterials 2020 Oct;266():120435
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, et al
J Extracell Vesicles 2020 Aug;9(1):1800222
Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule - single vesicle level by fluorescence correlation spectroscopy and single particle imaging.
Corso G, Heusermann W, Trojer D, Görgens A, Steib E, Voshol J, et al
J Extracell Vesicles 2019 ;8(1):1663043
Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material.
Görgens A, Bremer M, Ferrer-Tur R, Murke F, Tertel T, Horn PA, et al
J Extracell Vesicles 2019 ;8(1):1587567
The viral protein corona directs viral pathogenesis and amyloid aggregation.
Ezzat K, Pernemalm M, Pålsson S, Roberts TC, Järver P, Dondalska A, et al
Nat Commun 2019 05;10(1):2331
Advances in therapeutic applications of extracellular vesicles.
Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S
Sci Transl Med 2019 May;11(492):
Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography.
Corso G, Mäger I, Lee Y, Görgens A, Bultema J, Giebel B, et al
Sci Rep 2017 09;7(1):11561
Functional Delivery of Lipid-Conjugated siRNA by Extracellular Vesicles.
O'Loughlin AJ, Mäger I, de Jong OG, Varela MA, Schiffelers RM, El Andaloussi S, et al
Mol. Ther. 2017 07;25(7):1580-1587
Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER.
Heusermann W, Hean J, Trojer D, Steib E, von Bueren S, Graff-Meyer A, et al
J. Cell Biol. 2016 04;213(2):173-84
Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties.
Nordin JZ, Lee Y, Vader P, Mäger I, Johansson HJ, Heusermann W, et al
Nanomedicine 2015 May;11(4):879-83
Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting.
Wiklander OP, Nordin JZ, O'Loughlin A, Gustafsson Y, Corso G, Mäger I, et al
J Extracell Vesicles 2015 ;4():26316
Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers.
Goyenvalle A, Griffith G, Babbs A, El Andaloussi S, Ezzat K, Avril A, et al
Nat. Med. 2015 Mar;21(3):270-5
Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles.
Li J, Lee Y, Johansson HJ, Mäger I, Vader P, Nordin JZ, et al
J Extracell Vesicles 2015 ;4():26883
Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides.
Hammond SM, McClorey G, Nordin JZ, Godfrey C, Stenler S, Lennox KA, et al
Mol Ther Nucleic Acids 2014 Nov;3():e212
Extracellular vesicles: biology and emerging therapeutic opportunities.
EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ
Nat Rev Drug Discov 2013 May;12(5):347-57
Exosome-mediated delivery of siRNA in vitro and in vivo.
El-Andaloussi S, Lee Y, Lakhal-Littleton S, Li J, Seow Y, Gardiner C, et al
Nat Protoc 2012 Dec;7(12):2112-26
A peptide-based vector for efficient gene transfer in vitro and in vivo.
Lehto T, Simonson OE, Mäger I, Ezzat K, Sork H, Copolovici DM, et al
Mol. Ther. 2011 Aug;19(8):1457-67
Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo.
Andaloussi SE, Lehto T, Mäger I, Rosenthal-Aizman K, Oprea II, Simonson OE, et al
Nucleic Acids Res. 2011 May;39(9):3972-87
Research in media
Tiny bubbles can be future treatment for inflammation
Scientists hope that tiny sacs of material excreted by cells – so-called extracellular vesicles – can be used to deliver drugs inside the body. Researchers at Karolinska Institutet now show that these nano-bubbles can transport protein drugs that reduce inflammation caused by different diseases. The technique, which is presented in Nature Biomedical Engineering, shows promising results in animal models.