Abstract 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. CRISPRCas CRISPR Cas However purposes healthrelated health related addition ClinicalTrialsgov ClinicalTrials gov 66 nonduplicated non duplicated extracted 22 not ninetytwo ninety two detail 9 these 50 institutions diseases cancer neurological disorders metabolism ophthalmological hematological advancing field 6 2 5

Abstract 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.