Publications
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Muscling through AAV immunity. Vrije Universiteit Brussel
AAV-1 is one of the most promising vectors for gene delivery to skeletal muscle. In this issue of Blood, Mingozzi and colleagues now demonstrate that AAV-1-mediated gene transfer into human skeletal muscle results in activation of capsid-specific T cells.
Intraparenchymal convection enhanced delivery of AAV in sheep to treat Mucopolysaccharidosis IIIC KU Leuven
BACKGROUND: Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an ...
Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants KU Leuven Vrije Universiteit Brussel
Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation ...
Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints KU Leuven
Vectors based on the adeno-associated virus (AAV) are attractive and versatile vehicles for in vivo gene transfer. The virus capsid is the primary interface with the cell that defines many pharmacological, immunological and molecular properties. Determinants of these interactions are often restricted to a limited number of capsid amino acids. In this study, a portfolio of novel AAV vectors was developed after a structure-function analysis of ...
Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders KU Leuven Vrije Universiteit Brussel
Bioengineering of viral vectors for therapeutic gene delivery is a pivotal strategy to reduce doses, facilitate manufacturing, and improve efficacy and patient safety. Here, we engineered myotropic adeno-associated viral (AAV) vectors via a semirational, combinatorial approach that merges AAV capsid and peptide library screens. We first identified shuffled AAVs with increased specificity in the murine skeletal muscle, diaphragm, and heart, ...
Three-dimensional multipotent progenitor cell aggregates for expansion, osteogenic differentiation and 'in vivo' tracing with AAV vector serotype 6 KU Leuven
Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells with a high growth rate suitable for therapeutical applications as three-dimensional (3D) aggregates. Combined applications of osteogenically differentiated MAPC (OD-MAPC) aggregates and adeno-associated viral vectors (AAV) in bone bioengineering are still deferred until information with regard to expansion technologies, osteogenic potential, and AAV cytotoxicity and ...
Treatment of Infantile-Onset Pompe Disease in a Rat Model with Muscle-Directed AAV Gene Therapy Vrije Universiteit Brussel
OBJECTIVE: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD. Mouse models of PD do not completely reproduce human IOPD severity. Our main objective was to generate the first IOPD rat model to assess an ...