Daniel Simão was awarded with the Best Young Scientist Oral Presentation

Daniel Simão, researcher from the Animal Cell Technology Unit (iBET/ITQB NOVA), was awarded with the Best Young Scientist Oral Presentation at the 19th Congress of the European Society of Toxicology in vitro (ESTIV) held in Juan-les-Pins, France (17-20 October). ESTIV is the leading organization in Europe that promotes and strengthens the scientific network in the field of in vitro toxicology and of alternatives to animal experimentation. This conference focused on the novel developments and technologies that can strengthen the interpretation and application of in vitro methods in risk assessment. The awarded work authored by Daniel Simão, Catarina Pinto, Paulo Fernandes, Isabella Saggio, Lucy Collinson, Giampietro Schiavo, Eric Kremer, Paula Alves and Catarina Brito was entitled “Towards improving predictability in pre-clinical research: human 3D neural in vitro model for assessment of gene therapy vectors”. In this work a novel human 3D neural model was developed, based on the differentiation of human neural stem cells as cell aggregates (neurospheres) in agitation-based culture systems. This strategy generated complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. An extensive toolbox of analytical methodologies has been adapted to 3D neural cell models, allowing molecular and phenotypic profiling and interrogation. The developed model was employed for efficacy and safety assessment of helper-dependent canine adenovirus type 2 vectors (hd-CAV2) as candidates for gene therapy applications. Under optimized conditions, hd-CAV2 transduction led to stable long-term transgene expression with minimal toxicity. These vectors preferentially transduced neurons, in contrast to the widely used human adenovirus type 5 (HAdV5) that showed increased tropism towards glial cells. The presented data demonstrated that hd-CAV2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity. This work was developed within the scope of the European Union project BrainCAV (FP7-222992), in collaboration with the Institut de Génétique Moléculaire de Montpellier, Università di Roma La Sapienza and Cancer Research UK.