In vivo site-specific engineering to reprogram human T cells
February 18, 2025 @ 15:15 – 16:15 CET
Spotlight seminar series welcomes the newly recruited SciLifeLab Fellow William Nyberg to present his research in Air&Fire Campus Solna on February 18th.
William Nyberg, PhD, is a newly appointed principal investigator at the Karolinska Institute. Building on scientific discoveries as a postdoc in Justin Eyquem’s research lab at UCSF, his lab focuses on reprogramming T cells in vivo using advanced genetical engineering for therapeutic purposes. This is done primarily with the use of CARs, but are also exploring the use of other synthetic receptors and therapeutic TCR sequences to develop new T cell therapies against cancers. In 2023, he was honored with the Excellence in Research Award by the ASGCT and joined the Karolinska Institute and Science for Life Laboratory in 2024 to pursue his research.
Abstract
Engineered T cells, reprogrammed to express chimeric antigen receptors (CAR) or T cell receptors (TCR), have transformed cancer treatment and are being explored as therapeutics for autoimmune disorders and infectious diseases. Enhancing T cell function through genome editing—either by disrupting endogenous genes or precisely inserting DNA payloads—has shown significant promise. However, the ex vivo manufacturing process is lengthy, costly, and requires pre-conditioning, limiting the accessibility of these therapies. In vivo generation of CAR-T cells could overcome these barriers. In this presentation, I will demonstrate that stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads. We developed a two-vector system to deliver CRISPR-Cas9 ribonucleoproteins (RNPs) and a DNA donor template, using enveloped delivery vehicles (EDVs) and adeno-associated virus (AAVs), respectively. By integrating a CAR transgene into a T cell-specific locus we generated therapeutic levels of CAR-T cells in a humanized mouse model in vivo. These findings offer a promising pathway to more efficient, precise, and widely accessible T cell therapies.
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