The safety, immunogenicity, and efficacy of a vaccine against cutaneous leishmaniasis in rural Ecuadorian children was assessed in a randomized, controlled, double-blinded study. Vaccine group subjects received 2 intradermal doses of a whole, killed promastigote vaccine cocktail plus bacille Calmette-Guérin (BCG) adjuvant. Control subjects got 2 doses of BCG only. The subjects who received both vaccination doses, 438 in the vaccine group (79.3%) and 406 in the control group (83.4%), were followed for 12 months. No serious adverse side effects were identified in either group. Significantly more vaccine group subjects than controls converted to a positive Montenegro skin test (85.1% vs. 20.1%; chi2 = 279; P < .001). The incidence of cutaneous leishmaniasis was significantly reduced in the vaccine compared with the control group (2.1% vs. 7.6%; chi2 = 8.95; P < .003). The protective efficacy of the vaccine was 72.9% (95% confidence interval = 36.1%-88.5%).

Diseases caused by alterations in the DNA can be overcome by providing the cells or tissues with a functional copy of the mutated gene. The most common form of gene therapy implies adding an extra genetic unit into the cell. However, new genome engineering techniques also allow the modification or correction of the existing allele, providing new possibilities, especially for dominant diseases. Gene therapies have been tested for 30 years in thousands of clinical trials, but presently, we have only three authorised gene therapy products for the treatment of inherited diseases in European Union. Here, we describe the gene therapy alternatives already on the market in the European Union and expand the scope to some clinical trials. Additionally, we discuss the ethical and regulatory issues raised by the development of these new kinds of therapies. Keywords CRISPR-Cas9. Gene therapy. Genetic engineering This article is part of topical collection on Rare Diseases

Summary Human induced pluripotent stem cells (hiPSCs) allow in vitro study of genetic diseases and hold potential for personalized stem cell therapy. Gene editing, precisely modifying specifically targeted loci, represents a valuable tool for different hiPSC applications. This is especially useful in monogenic diseases to dissect the function of unknown mutations or to create genetically corrected, patient-derived hiPSCs. Here we describe a highly efficient method for simultaneous base editing and reprogramming of fibroblasts employing a CRISPR-Cas9 adenine base editor. As a proof of concept, we apply this approach to generate gene-edited hiPSCs from skin biopsies of four patients carrying a Finnish-founder pathogenic point mutation in either NOTCH3 or LDLR genes. We also show LDLR activity restoration after the gene correction. Overall, this method yields tens of gene-edited hiPSC monoclonal lines with unprecedented efficiency and robustness while considerably reducing the cell culture time and thus the risk for in vitro alterations.

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