Biomolecular Medicine and Advanced therapies- focus on delivery of RNA therapeutics – 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.

Our research

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 acid therapeutics for gene therapy of diseases including muscular dystrophies and neurodegenerative disorders. 

We develop innovative and efficient drug delivery technologies that are able to carry protein and/or gene therapies to the target tissues safely and efficiently. Our particular emphasis lies on natural nanocarriers, bioengineered extracellular vesicles (EVs), and synthetic nanoparticles, such as cell-penetrating peptides (CPPs) and lipid nanoparticles (LNPs). 

My team investigates EV engineering to encapsulate siRNA, mRNA, proteins, and genome-editing tools, and modifying their surfaces for precise tissue targeting. We have developed state-of-the-art platforms for both exogenous cargo loading and scaffold-based endogenous loading, improving encapsulation efficiency and functional delivery. With this, we have demonstrated targeted EV delivery in the brain, to tumors, and extrahepatic organs in vivo. Moreover, our portfolio for streamlined nanoparticle characterization methods, including advanced single-vesicle flow cytometry, and profound experience in EV-based biomarker analysis positions our group at the forefront of the EV research field. 

In parallel, my group is advancing complementary delivery platforms that include synthetic CPP- and LNP-based technologies as well as precision bioconjugation strategies for extrahepatic targeting of oligonucleotides. Within the newly established ATMP Center at Karolinska Institutet, we are exploring the design, formulation, and functionalization of CPPs, LNPs, and antibody- or ligand-conjugated oligonucleotides. With our fully integrated team of organic chemists and biologists, we tailor these nanoparticles to achieve specific tissue tropisms and integrate targeting and endosomal escape strategies to overcome delivery bottlenecks in RNA and DNA delivery. These efforts include our combinatorial “in-situ engineering” strategy, where synthetic nanoparticles transiently reprogram host cells to secrete therapeutic EVs, creating hybrid delivery workflows.

Operating at the intersection of advanced nanomedicine research and translational development, my lab bridges mechanistic studies with preclinical models and industry collaborations. Our work aims to build a versatile and adaptable toolkit for therapeutic payload delivery and various disease targets.

External funding

Swedish Research Council (Vetenskåpsrådet), Novo Nordisk Foundation, ERC Consolidator, DELIVER, Horizon H2020 EXPERT, Sjöberg stiftelse, Flagship Grant, Swedish Foundation for Strategic Research (SSF), Swedish Cancer Foundation (Cancerfonden), Swedish Childhood Cancer Foundation (Barncancerfonden), Swedish Brain Foundation (Hjärnfonden), Knut and Alice Wallenberg Foundation, Vinnova, Evox Therapeutics, UK Research and Innovation, Medical Research Council (MRC), KI internal funding (CIMED, KID, KI faculty funding.

Research in media

Publications

Selected publications

Funding

Grants

  • 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.
  • Swedish Research Council
    1 January 2021 - 31 December 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
  • Swedish Research Council
    1 January 2016 - 31 December 2019

Staff and contact

Group leader

All members of the group

Keywords:
Cell and Molecular Biology Medical Biotechnology (Focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Medicinal Chemistry (Natural Sciences at 10405) Nanotechnology for/in Life Science and Medicine
Content reviewer:
25-09-2025