Biology subjects

Salameh, M.

Publications and source records attributed to Salameh, M..

3 recordsLinked to original sources

bioRxiv2026

Single anticodon-edited tRNA therapy targeting highly prevalent Arg>Ter premature termination codons causing inherited retinal diseases

Nonsense variants cause 18% of inherited retinal diseases (IRDs), yet current therapies require variant-specific development, leaving most patients untreated. Here, we combined a large-scale genetic analysis literature survey of >37,500 IRD patients with anticodon-edited (ACE)-tRNA engineering to create a single, gene-agnostic therapy targeting Arg>Ter nonsense variants which are the most prevalent subclass (35%) of premature stop codons (PTCs). We developed an optimized ACE-tRNA (V3) that achieved up to 86% readthrough across 13 clinically relevant variants, restored native PRCD localization in the arRP-causing p.R22* mutant, and demonstrated activity in photoreceptor-like cells. To enable translation, we established an AAV2/7m8 production platform (1*10{superscript 1}{superscript 2}-1*10{superscript 1}3 GC/mL) and defined 1*10 GC/eye as the safe dose in mice. This patient genetics-guided strategy positions ACE-tRNA_V3 as a promising candidate for preclinical development, offering a precision medicine approach that targets the most common nonsense variant class with a single therapeutic molecule.

genetics↗

bioRxiv2022

A receptor-independent signaling pathway for BDNF

In addition to its well-known receptor-mediated function in cell survival, differentiation and growth, we report that the extracellular brain-derived neurotrophic factor (BDNF) also controls the intracellular KEAP1-NRF2 cytoprotective system by a receptor-independent pathway. Extracellular BDNF can cross the cell membrane as it possesses a protein-translocation domain, also known as cell-penetrating peptide. This membrane crossing process is energy-independent, ruling out endocytosis and receptor-dependent mechanisms. Once in the cytosol, BDNF binds to KEAP1 with a nanomolar affinity, enabling nuclear translocation of NRF2 and transcription of NRF2-target genes. BDNF is thus a major regulator of NRF2 activation. A dysfunction of this BDNF-KEAP1-NRF2 pathway may be involved in most diseases where antioxidant and cytoprotective functions are altered. This novel form of communication, whereby a receptor ligand protein exerts a biological activity by crossing the cell membrane, opens new avenues for cell signaling.

cell biology↗

bioRxiv2019

Investigating Biomechanical Properties of A. tortilis as Related to their Habitat

The biomechanical properties of Acacia tortilis were investigated considering its habitat (wild vs. nursery). The plant materials were collected from partially urbanized area in Doha city and from Qatar Foundation Nursery. The results show that Acacia grown in field are more flexible than those grown in nursery. Youngs Modulus of Elasticity was found to be 191 MPa and 617 MPa and the Flexural Modulus was found to be 49 MPa and 575 MPa and the breaking force was found to be 210 and 550 N for nursery and field Acacia, respectively. The deflection angle was measured using sensitive flex sensors connected to Arduino boards and was found to be higher for field Acacia (50{circ}). Image processing techniques were used to mathematically describe the branch motion versus time diagrams.\n\nThe plant part being investigated was covered with red tape and videotaped while subjected to a force causing it to bend. The stem was divided into 745 successive points and the change in their position with time taken frame by frame was converted into a change in position expressed through mathematical parameters. The bending movement of the branch was found to follow a power function H = (4001 - e0.06m).\n\nHighlightField grown Acacia have higher values of Youngs and Flexural Moduli than nursery grown ones thus conferring them more elasticity and flexibility.

plant biology↗