Adenovirus type 6: Subtle structural distinctions from adenovirus type 5 result in essential differences in properties and perspectives for gene therapy

Margarita Romanenko, Ivan Osipov, Sergey V. Netesov, Julia Davydova

Research output: Contribution to journalReview articlepeer-review

Abstract

Adenovirus vectors are the most frequently used agents for gene therapy, including on-colytic 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 ham-pers 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 on-colytic 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.

Original languageEnglish (US)
Article number1641
JournalPharmaceutics
Volume13
Issue number10
DOIs
StatePublished - Oct 2021

Bibliographical note

Funding Information:
Funding: This study was supported by NIH NCI R01CA174861 (JD); NIH NCI R01CA228760 (JD); and the FSUS-2020-0035 grant from Russian Ministry of Science and Higher Education (SN).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Ad5
  • Ad6
  • Adenovirus
  • Immunother-apy
  • Kupffer cells
  • Liver tropism
  • Oncolytic viruses
  • Serotype 6
  • Vaccine
  • Virotherapy

PubMed: MeSH publication types

  • Journal Article
  • Review

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