CRISPR/Cas patents and health-related publications in South America.

CRISPR/Cas is being increasingly used for various applications. However, different countries introduce new technologies at different paces and purposes. This study reviews research progress using the CRISPR/Cas system in South America, focusing on health-related applications. The PubMed database was used to identify relevant articles about gene editing with CRISPR/Cas, whereas patents were searched in the Patentscope database. In addition, ClinicalTrials.gov was used to find information on active and recruiting clinical trials. A total of 668 non-duplicated articles (extracted from PubMed) and 225 patents (not all health-related) were found. One hundred ninety-two articles on health-related applications of CRISPR/Cas were analyzed in detail. In 95 out of these, more than 50% of the authors were affiliated with South American institutions. Experimental CRISPR/Cas studies target different diseases, particularly cancer, neurological, and endocrine disorders. Most patents refer to generic applications, but those with clear disease indications are for inborn errors of metabolism, ophthalmological, hematological, and immunological disorders. No clinical trials were found involving Latin American countries. Although research on gene editing in South America is advancing, our data show the low number of national innovations protected by intellectual property in this field.

Gene editing strategies to treat lysosomal disorders: The example of mucopolysaccharidoses.

Lysosomal storage disorders are a group of progressive multisystemic hereditary diseases with a combined incidence of 1:4,800. Here we review the clinical and molecular characteristics of these diseases, with a special focus on Mucopolysaccharidoses, caused primarily by the lysosomal storage of glycosaminoglycans. Different gene editing techniques can be used to ameliorate their symptoms, using both viral and nonviral delivery methods. Whereas these are still being tested in animal models, early results of phase I/II clinical trials of gene therapy show how this technology may impact the future treatment of these diseases. Hurdles related to specific hard-to-reach organs, such as the central nervous system, heart, joints, and the eye must be tackled. Finally, the regulatory framework necessary to advance into clinical practice is also discussed.

Protection is not always a good thing: The immune system's impact on gene therapy.

There are many clinical trials underway for the development of gene therapies, and some have resulted in gene therapy products being commercially approved already. Significant progress was made to develop safer and more effective strategies to deliver and regulate genetic products. An unsolved aspect is the immune system, which can affect the efficiency of gene therapy in different ways. Here we present an overview of approved gene therapy products and the immune response elicited by gene delivery systems. These include responses against the vector or its content after delivery and against the product of the corrected gene. Strategies to overcome the hurdles include hiding the vector or/and the transgene product from the immune system and hiding the immune system from the vector/transgene product. Combining different strategies, such as patient screening and intelligent vector design, gene therapy is set to make a difference in the life of patients with severe genetic diseases.