Establishment and Characterization of a Stable Producer Cell Line Generation Platform for the Manufacturing of Clinical-Grade Lentiviral Vectors.

To date, nearly 300 lentiviral-based gene therapy clinical trials have been conducted, with eight therapies receiving regulatory approval for commercialization. These advances, along with the increased number of advanced-phase clinical trials, have prompted contract development and manufacturing organizations (CDMOs) to develop innovative strategies to address the growing demand for large-scale batches of lentiviral vectors (LVVs). Consequently, manufacturers have focused on optimizing processes under good manufacturing practices (GMPs) to improve cost-efficiency, increase process robustness, and ensure regulatory compliance.

Abolishing Retro-Transduction of Producer Cells in Lentiviral Vector Manufacturing.

Transduction of producer cells during lentiviral vector (LVV) production causes the loss of 70-90% of viable particles. This process is called retro-transduction and it is a consequence of the interaction between the LVV envelope protein, VSV-G, and the LDL receptor located on the producer cell membrane, allowing lentiviral vector transduction. Avoiding retro-transduction in LVV manufacturing is crucial to improve net production and, therefore, the efficiency of the production process.

Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality.

Background And Objective: The definition of pre-capillary pulmonary hypertension (PH) has been modified, with lowering of the mean pulmonary arterial pressure (mPAP) threshold from 25 to 20 mmHg and addition of a mandatory criterion of pulmonary vascular resistance (PVR) ≥ 2 Wood units (WU). Our objectives were: 1/ to estimate the proportion of patients reclassified as having pre-capillary PH when using the new 2022 ESC/ERS hemodynamic criteria (i.e.

Dual-energy CT lung perfusion characteristics in pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH): preliminary experience in 63 patients.

Background: In the stratification of potential causes of PH, current guidelines recommend performing V/Q lung scintigraphy to screen for CTEPH. The recognition of CTEPH is based on the identification of lung segments or sub-segments without perfusion but preserved ventilation. The presence of mismatched perfusion defects has also been described in a small proportion of idiopathic pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH).