Current Progress in Therapeutic Gene Editing for Monogenic Diseases

Programmable nucleases allow defined alterations in the genome with ease-of-use, efficiency, and specificity. Their availability has led to accurate and widespread genome engineering, with multiple applications in basic research, biotechnology, and therapy. With regard to human gene therapy, nuclease-based gene editing has facilitated development of a broad range of therapeutic strategies based on both nonhomologous end joining and homology-dependent repair. This review discusses current progress in nuclease-based therapeutic applications for a subset of inherited monogenic diseases including cystic fibrosis, Duchenne muscular dystrophy, diseases of the bone marrow, and hemophilia and highlights associated challenges and future prospects

Clinical applications of gene therapy for rare diseases: A review

Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and β-thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases

Spinal Muscular Atrophy: A Rare but Treatable Disease of the Nervous System

When something is rare it means that it happens very infrequently. Did you know that most diseases are rare? There are more than 6,000 known rare diseases, each affecting fewer than 1 in every 2,000 people. But if we put all the rare diseases together, they affect about 1 in 17 of us! Given that they are individually uncommon, rare diseases are often poorly understood. However, rare diseases have a large impact on families and society, thus they require increased attention. In this article, we will explore a rare disease of the nervous system called spinal muscular atrophy (SMA). We will tell you about the symptoms of SMA and explain how it is inherited. SMA has led the way in the discovery of treatments for rare diseases. Finding treatments for rare diseases requires intensive research and commitment from many people, but the success of SMA treatments highlights the importance of studying other rare conditions

Evaluating Urban Regeneration Policies. Methodological Proposal to Delimitate Experimental and Equivalent Urban Areas

El presente artículo presenta una propuesta metodológica para la delimitación de áreas territoriales aplicando una estrategia de corte cuasi-experimental, comparando las áreas en las que se ha desarrollado algún proyecto de regeneración urbana llamadas “áreas experimentales” con otras similares en las que no se ha desarrollado ningún proyecto, denominadas “áreas equivalentes”. Esta metodología es el paso previo necesario para el análisis de los efectos de los programas de regeneración urbana, que permitirá posteriormente comparar la evolución en el tiempo de pares semejantes entre sí (área experimental y área equivalente). En primer lugar, se explica el objetivo que subyace a la delimitación de estas áreas territoriales. En segundo lugar, se describe la metodología utilizada para seleccionar las áreas equivalentes. En tercer lugar, se presentan los resultados, esto es, la delimitación de áreas experimentales y equivalentes. . Por último, mediante procedimientos estadísticos concretos, análisis de varianza o ANOVA de un factor, se validan los resultados obtenidos. El trabajo se centra en las ciudades andaluzas de más de 100 mil habitantes en las que se han ejecutado proyectos de regeneración urbana.This article analyses a methodological proposal for the delimitation of territorial areas applying a quasi-experimental strategy, comparing areas where projects have been developed based in urban regeneration called “experimental areas” with similar ones without any project, called “equivalent areas”. This methodology is a necessary previous step to analyze the effect of programs about urban regeneration, which will allow subsequently to compare the evolution of similar pairs among themselves (experimental and equivalent areas). Firstly, we explain the underlying objective of delimitation in these territorial areas. Secondly, the methodology used to select the equivalent areas is described. Thirdly, the results are presented, it means, the delimitation of experimental and equivalent areas. Finally, through means of specific statistical procedures, analysis of variance or ANOVA of a factor, the obtained results are validated. The work is focused on Andalusian cities with a population over 100.000 inhabitants in which urban regeneration projects have been implemented.Consejería de Fomento y Vivienda de la Junta de Andalucía GGI30011/DIYFEDER GGI30011/DI