Artikel ; Online: Adenoviral Gene Therapy Vectors in Clinical Use-Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety.
International journal of molecular sciences
2023 Band 24, Heft 22
Abstract: Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication- ... ...
Abstract | Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required. To render adenoviruses replication deficient, their genomic E1 region is deleted. However, it has been known for a long time that during their propagation, some viruses will regain their replication capability by recombination in production cells, most commonly HEK293. Recently developed RCA assays have revealed that many clinical batches contain more RCA than previously assumed and allowed by regulatory authorities. The clinical significance of the higher RCA content has yet to be thoroughly evaluated. In this review, we summarize the biology of adenovirus vectors, their manufacturing methods, and the origins of RCA formed during HEK293-based vector production. Lastly, we share our experience using minimally RCA-positive serotype 5 adenoviral vectors based on observations from our clinical cardiovascular gene therapy studies. |
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Mesh-Begriff(e) | Humans ; Adenoviridae/genetics ; HEK293 Cells ; Genetic Vectors/genetics ; Genetic Therapy/adverse effects ; Genetic Therapy/methods ; Virus Replication/genetics |
Sprache | Englisch |
Erscheinungsdatum | 2023-11-20 |
Erscheinungsland | Switzerland |
Dokumenttyp | Journal Article ; Review |
ZDB-ID | 2019364-6 |
ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
ISSN (online) | 1422-0067 |
ISSN | 1422-0067 ; 1661-6596 |
DOI | 10.3390/ijms242216519 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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