Biology subjects

Jaulin, N.

Publications and source records attributed to Jaulin, N..

3 recordsLinked to original sources

bioRxiv2026

Engineered muscle tissues with enhanced maturation enable the identification of clinically relevant rAAV capsids

Developing in vitro models that recapitulate both the structure and function of native human tissues is crucial for a better understanding of pathophysiology and for improving the reliability of preclinical studies. Here, we demonstrate that engineered muscle tissues derived from human pluripotent stem cells can serve as an in vitro platform for gene therapy. Recombinant vectors derived from the adeno-associated virus transduce engineered muscle tissues with high efficiency and in a dose-dependent manner, allowing long term assessment of transgene expression in a human cellular context. We next used this model to conduct a comparative analysis of 8 natural AAV capsids and showed that their relative efficiency depends on engineered muscle tissue maturation level. In more mature tissues subjected to uniaxial mechanical stretch, AAV9 performed better, which is reminiscent of its high clinical potential in patients with neuromuscular disorders. Finally, our model also confirmed the higher efficiency of artificial MyoAAV variants specifically developed to have an improved muscle transduction. Altogether, this work demonstrates the potential of human engineered muscle tissues in the preclinical testing of AAV vectors, paving the way for the development of personalized gene therapy platforms.

bioengineering↗

bioRxiv2025

Ultrafast tyrosine-based cell membrane modification via diazonium salts: a new frontier for biomedical applications

In this study, we present an ultrafast, efficient, and broadly applicable strategy for cell membrane modification via tyrosine bioconjugation using diazonium salt derivatives. This chemical approach enables both one-step and two-step functionalization of adherent, suspension, and primary cells with diverse ligands, including imaging probes, carbohydrates, biotin, and proteins, without inducing cytotoxicity or immune activation. Membrane engineering through bioconjugation is emerging as a valuable tool in biomedical research, given the cell membranes central role in signaling, transport, and cell-cell interactions. Compared to traditional glyco-engineering methods that often require multiday incubations and can cause cellular stress, our approach achieves precise and high-density grafting in less than one hour, with improved reproducibility and biological compatibility. Importantly, we demonstrate that this strategy can be applied to a variety of cell types, encompassing both immortalized cell lines and primary cells, notably Peripheral Blood Mononuclear Cells (PBMCs) and human effector cells such as natural killer (NK) cells, to enhance their cytotoxic function against EGFR-positive cancer cells via surface-conjugated Nanofitin. Moreover, we show that the bioconjugated signal diminishes over time due to cell division, offering a self-limiting alternative to permanent genetic modifications such as CAR-T, thereby mitigating risks associated with overly prolonged immune activation. Finally, the feasibility of storing pre-functionalized cells at -80 {degrees}C expands the practicality of this platform for future ready-to-use applications. Together, these features make our method a compelling alternative to current technologies for applications in targeted therapy, diagnostics, and cell-based immunotherapy.

bioengineering↗

bioRxiv2023

Prevalence study of cellular capsid-specific immune responses to AAV1, 2, 4, 5, 8, 9 and rh10 reveals particular features for AAV9

Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors for in vivo gene transfer as illustrated by the approvals of 7 drugs across Europe and the USA. Nevertheless, pre-existing immunity to AAV capsid in humans remains one of the major limits for a successful clinical translation. Whereas pre-existing humoral response to AAV capsid is well documented, the prevalence of pre-existing capsid-specific T cell responses still needs to be studied and characterized. Here, we investigated the prevalence of AAV-specific circulating T cells towards AAV2, 4, 5, 8, 9 and rh10 in a large cohort of healthy donors using the standard IFN{gamma} ELISpot assay. We observed the highest prevalence of pre-existing cellular immunity to AAV9 serotype followed by AAV8, AAV4, AAV2, AAVrh10 and AAV5 independently of the donors serological status. An in-depth analysis of T cell responses towards the 2 most prevalent serotypes 8 and 9 shows that IFN{gamma} secretion is mainly mediated by CD8 T cells for both serotypes. A polyfunctional analysis reveals different cytokine profiles between AAV8 and AAV9. Surprisingly, no IL-2 secretion was mediated by anti-AAV9 immune cells suggesting that these cells may rather be exhausted or terminally differentiated than cytotoxic T cells. Altogether, these results suggest that pre-existing immunity to AAV may vary depending on the serotype and support the necessity of using multiparametric monitoring methods to better characterize anti-capsid cellular immunity and foresee its impact in rAAV-mediated clinical trials.

immunology↗