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Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy

期刊

PHARMACEUTICS
卷 13, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/pharmaceutics13101641

关键词

adenovirus; serotype 6; Ad6; Ad5; oncolytic viruses; virotherapy; vaccine; immunotherapy; Kupffer cells; liver tropism

资金

  1. NIH NCI
  2. NIH NCI
  3. Russian Ministry of Science and Higher Education

向作者/读者索取更多资源

Adenovirus type 6 (HAdV-C6) shows promise in gene therapy, especially in vaccine and anticancer drug development. Compared to HAdV-C5, HAdV-C6 differs structurally and immunogenically, enabling evasion of specific immune cells uptake and influencing overall distribution after systemic administration.
Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It's hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed on adenovirus platform. The vast majority of adenoviral vectors are based on the most studied human adenovirus type 5 (HAdV-C5), however, its immunogenicity often hampers the clinical translation of HAdV-C5 vectors. The search of less seroprevalent adenovirus types led to another species C adenovirus, Adenovirus type 6 (HAdV-C6). HAdV-C6 possesses high oncolytic efficacy against multiple cancer types and remarkable ability to induce the immune response towards carrying antigens. Being genetically very close to HAdV-C5, HAdV-C6 differs from HAdV-C5 in structure of the most abundant capsid protein, hexon. This leads to the ability of HAdV-C6 to evade the uptake by Kupffer cells as well as to distinct opsonization by immunoglobulins and other blood proteins, influencing the overall biodistribution of HAdV-C6 after systemic administration. This review describes the structural features of HAdV-C6, its interaction with liver cells and blood factors, summarizes the previous experiences using HAdV-C6, and provides the rationale behind the use of HAdV-C6 for vaccine and anticancer drugs developments.

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