Assessment of cell-binding capacity of shed rAAV particles after gene therapy vector administration: implications for environmental risk and hygiene recommendations.
IF 3.6 3区 医学Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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引用次数: 0
Abstract
Background: Currently, adeno-associated viruses (AAVs) are the most commonly used in vivo gene therapy (GT) vector platform. Risks posed to the environment, including the public, have not been well studied in the past. There is uncertainty concerning the necessary level of biocontainment and appropriate hygiene behavior for the handling of secreta/excreta of GT patients during the shedding phase.
Research design and methods: Here, feces and urine samples from non-human primates, treated with an AAV9-based vector at 2 × 1013 vector genomes per kilogram body weight (vg/kg), were analyzed for vector presence and subsequently analyzed for their capacity to bind to cells.
Results: Both sample types contained particles which bound to cells at concentrations in the range of ~104 (and higher) vg/mL of culture medium. Novel control rAAV vector displayed a ~2-3 orders of magnitude higher affinity to cells than shed particles.
Conclusions: The lower binding capacity of the shed vector particles speaks in favor of a more relaxed containment and hygiene approach in the context of GT. It is recommended that current hygiene and contact-avoidance-based containment measures after GT administration are reduced. The results also support the efforts to achieve a simplification of the regulatory review process of medicinal genetically modified organisms.
期刊介绍:
Expert Opinion on Biological Therapy (1471-2598; 1744-7682) is a MEDLINE-indexed, international journal publishing peer-reviewed research across all aspects of biological therapy.
Each article is structured to incorporate the author’s own expert opinion on the impact of the topic on research and clinical practice and the scope for future development.
The audience consists of scientists and managers in the healthcare and biopharmaceutical industries and others closely involved in the development and application of biological therapies for the treatment of human disease.
The journal welcomes:
Reviews covering therapeutic antibodies and vaccines, peptides and proteins, gene therapies and gene transfer technologies, cell-based therapies and regenerative medicine
Drug evaluations reviewing the clinical data on a particular biological agent
Original research papers reporting the results of clinical investigations on biological agents and biotherapeutic-based studies with a strong link to clinical practice
Comprehensive coverage in each review is complemented by the unique Expert Collection format and includes the following sections:
Expert Opinion – a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results;
Article Highlights – an executive summary of the author’s most critical points.