Transcriptome analysis of collagen VI-related muscular dystrophy muscle biopsies.

Objective: To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI-related muscular dystrophy (COL6-RD).

Methods: COL6-RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA-Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age- and sex-matched controls.

Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter.

Protection against epigenetic silencing is a desirable feature of future gene therapy vectors, in particular for those applications in which transgene expression will not confer growth advantage to gene-transduced cells. The ubiquitous chromatin opening element (UCOE) consisting of the methylation-free CpG island encompassing the dual divergently transcribed promoters of the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) has been shown to shield constitutive active heterologous promoters from epigenetic modifications and chromosomal position effects. However, it is unclear if this element can be used to improve expression from tissue-specific enhancer/promoters, while maintaining tissue specificity in hematopoietic cells.