Samir El Andaloussi

Samir El Andaloussi

Professor
Telephone: +46852483571
Mobile phone: +46737121613
Visiting address: Hälsovägen 7, Novum plan 5, 14157
Postal address: H5 Laboratoriemedicin, H5 BCM El Andaloussi, 141 52 Huddinge
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About me

  • Leader of exosome research. Professor of Biomolecular Medicine and Advanced Therapy at Karolinska Institutet since 1 November 2021.

Research

  • Research area/interest: Characterization and application of biological nanovesicles, exosomes, for drug delivery and development of novel oligonucleotide-based drugs to interfere with gene expression.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2029
    To date, there are no curative treatments for most neurodegenerative disorders, including synucleinopathies of the central nervous system (CNS) such as Parkinsons disease (PD). The greatest challenges in treating these are currently insufficient penetration of drugs to the parenchyma of the brain and achieving stable reduction of α-synuclein (SNCA) protein aggregation, the most significant hallmark of PD pathology. Therefore, it is imperative to find new solutions to these unmet medical needs. Recently, we have harnessed nature’s own nanoparticles, extracellular vesicles (EVs), for targeted delivery of biotherpeutics, with focus on Cas9-based gene editors. Here, we will establish a novel CNS delivery platform exploiting these engineered EVs for CRISPR/Cas9-mediated silencing of SNCA gene expression and prevention of α-synuclein aggregation. After optimization of EV engineering components focusing on enhanced cargo loading, gene editing, and EV delivery to deep brain parenchyma, we will demonstrate their therapeutic effect in models of PD by local injection into the brain of mice using osmotic pumps. If successful, this will open an entirely new avenue to treat PD and other synucleinopathies. Importantly, the modular nature of the EV engineering platform permits further adaptation to deliver other gene editors or drug modalities, thereby opening innovative possibilities to treat a range of CNS diseases.
  • Medical Research Council
    1 January 2025 - 31 December 2031
    Genome-targeted therapies, e.g., CRISPR-Cas9, use genetic sequence to target their actions to specific genes, bringing unrivalled specificity. This specificity will revolutionise healthcare, bringing therapies to previously untreatable rare disorders and precision gene- and cell-specific approaches to common disorders. By simply modifying the target sequence, a therapy can be retargeted to treat a new disorder. Our challenge is to unlock this potential, by developing 'Therapeutic Genomics' (TG), a genome-led, patient-centred, data-driven vision to bring genome-targeted therapies to the clinic, at scale. To achieve this challenge, our research aims to answer five major questions. First, which variants and which patients can be treated? We will develop computational and experimental methods to identify tractable genetic variants with different genome-targeted therapies. Applying these to genome sequencing data collected nationwide by researchers and the NHS, we will identify patients with correctable variants and symptoms appropriate to experimental therapies. Second, how can Therapeutic Platforms be developed and retargeted at scale to treat numerous genetic disorders? In collaboration with the laboratory that discovered CRISPR-Cas9 (UC Berkeley), we will develop exemplar Therapeutic Platforms and then retarget these to develop numerous therapies for other variants and disorders. Working with our industry partners, including Intellia and Danaher, we will develop high-throughput parallelized methods for measuring potency and safety in scalable cellular models, reducing the reliance on animal testing. Subsequent generations of Therapeutic Platforms and retargeting will extend therapies to more disorders. Third, how can Therapeutic Platform therapies be delivered effectively? At present, we lack a suitable vector for targeting neurons throughout the brain, a hurdle complicated by the inaccessibility of mature human neurons. Using cutting-edge technology to maintain human neuronal viability post-mortem, we will use directed evolution to develop brain-wide and cell-type-specific delivery systems, including viral, non-viral, and hybrid approaches. Fourth, how can insights from one therapy be used to improve the next therapy? By collecting data throughout our CoRE's research, we will apply artificial intelligence to refine our therapeutic and delivery technologies, ultimately developing safer and more effective therapies that treat an ever-expanding list of disorders. The data and algorithms from this work will be shared publicly to help design suitable therapies for all patients who need them. Fifth, how can we foster the research culture and clinical ecosystem to bring therapies to the clinic? Our research aims can only be achieved through a positive, inclusive research culture (e.g., openness, collaboration, teamwork, integrity, and diversity), and an interdisciplinary team. The MRC CoRE in TG will build on institutional initiatives to support culture change, embracing opportunities to enhance mentorship, teamwork, and communication. Key principles of Equality, Diversity, and Inclusion (EDI) and inclusive Public Patient Involvement and Engagement (PPIE) will be fully integrated into, and will enrich, the planning and execution of the CoRE's activities and governance. The MRC CoRE in TG will prime the clinical landscape required to bring genome-targeted therapies to the clinic, in collaboration with stakeholders and patients. Our team has the experience and facilities to secure additional funding and conduct first-in-human clinical trials. We will enlist UK infrastructure and industrial collaboration to reduce manufacturing costs and engage with the UK and other regulatory agencies to define workable standards for assessing Therapeutic Platforms. By developing urgently needed therapies for multiple rare disorders today, we will develop the expertise and capacity to better treat all rare and common disorders in the future.
  • Ming Wai Lau Centre for Reparative Medicine (MWLC)
    1 January 2024 - 31 December 2026
  • VINNOVA
    29 September 2023 - 30 June 2024
  • Platform development of innovative bioconjugates for cardiac delivery of antisense oligonucleotides
    Novo Nordisk Foundation (NNF)
    1 August 2023 - 1 August 2026
  • Knut och Alice Wallenberg Stiftelse (KAW)
    1 July 2023 - 31 December 2028
  • TransNAT: Transforming delivery, safety and efficacy of nucleic acid therapeutics: from intracellular uptake to targeting brain and muscle
    Medical Research Council
    1 November 2022 - 31 October 2025
  • UK Research and Innovation
    1 November 2022 - 31 October 2025
  • Cancerfonden
    1 January 2022 - 31 December 2024
  • EU-projekt DELIVER, Grant Agreement number 101001374
    European Research Council (ERC)
    1 March 2021 - 28 February 2026
  • European Research Council
    1 March 2021 - 28 February 2026
    Nucleic acid-based medicines have opened a new avenue in drug discovery to target currently undruggable genes and to express therapeutic proteins, unlocking novel therapeutic options for a range of diseases, including neurodegeneration. However, they need to be encapsulated in nanocarriers to ensure their stability and efficient uptake into cells and tissues. Synthetic nanoparticles based on cell-penetrating peptides (CPPs) and, particularly, lipid nanoparticles (LNPs) have recently emerged as potent vectors for hepatic delivery. However, these systems fail to robustly target other organs in a safe manner. Another promising nanocarrier for advanced drug delivery is extracellular vesicles (EVs) that have the ability to efficiently convey macromolecules into cells. As native nanoparticles, EVs benefit from immune tolerance as well as the ability to cross biological barriers to reach, for example, the brain. We have developed advanced strategies to bioengineer cells to generate EVs loaded with therapeutic RNAs and proteins. However, their production at scale is cumbersome and time consuming. Here, I propose a platform development using synthetic nanocarriers to transiently engineer hepatic cells in vivo and harness EVs to functionally DELIVER biotherapeutics to currently unreachable, distant organs, focusing on brain. To achieve this, genetic constructs will be developed that allow for transient in situ engineering of cells in vivo and release of cargo (e.g. CRE)- laden EVs, displaying CNS-specific peptides, that can be functionally transported to distant organs, including brain. We will exploit the same strategy using CPP-based nanoformulations, recently developed in my lab, injected locally in brain to secrete EVs loaded with the disease-relevant protein GBA1 as a treatment strategy for Parkinson´s disease. Long-term this novel project has enormous potential, as any engineered EV could be produced in situ and be used for delivery of virtually any biotherapeutics.
  • Development of modified extracellular vesicles for targeted delivery of RNA therapy
    Swedish Research Council
    1 January 2021 - 31 December 2025
  • Swedish Research Council
    1 January 2021 - 31 December 2024
  • US Army
    1 September 2020 - 31 March 2024
  • Muscle-Targeted Cell-Penetrating Peptides for Delivery of Cas9-RNPs and Modified mRNA to Dystrophic Muscle
    Congressionally Directed Medical Research Programs
    1 September 2020 - 31 August 2023
  • European Commission
    1 September 2019 - 28 February 2025
  • Swedish Foundation for Strategic Research (SSF)
    12 September 2017 - 31 December 2024
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • Biotechnology and Biological Sciences Research Council
    30 September 2015 - 31 March 2019
  • Medical Research Council
    31 August 2015 - 29 April 2021
  • Show more

Employments

  • Professor, Department of Laboratory Medicine, Karolinska Institutet, 2021-

Degrees and Education

  • Docent, Karolinska Institutet, 2018
  • Phd, Stockholm University, 2008
  • Examen i molekylär cellbiologi, Södertörn University, 2002

Visiting research fellowships

  • Research fellow at University of Oxford, 2013-2018
  • Postdocs at University of Oxford, 2011-2013
  • Postdocs, Karolinska Institutet, 2010-2012
  • Postdocs vid Stockholms universitet 2008–2010, 2008-2010

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