Chopping Down Trees vs. Sharpening the Axe – Balancing the Development of BPM Capabilities with Process Improvement

The management and improvement of business processes is an evergreen topic of organizational design. With many techniques and tools for process modeling, execution, and improvement being available, research pays progressively more attention to the organizational impact of business process management (BPM) and the development of BPM capabilities. Despite knowledge about the capabilities required for successful BPM, there is a lack of guidance on how these BPM capabilities should be developed and balanced with the improvement of individual business processes. As a first step to address this research gap, we propose a decision model that enables valuating and selecting BPM roadmaps, i.e., portfolios of scheduled projects with different effects on business processes and BPM capabilities. The decision model is grounded in the literature related to project portfolio selection, process performance measurement, and value-based management. We also provide an extensive demonstration example to illustrate how the decision model can be applied

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease