TY - JOUR

T1 - Adenovirus type 6: Subtle structural distinctions from adenovirus type 5 result in essential differences in properties and perspectives for gene therapy

AU - Romanenko, Margarita

AU - Osipov, Ivan

AU - Netesov, Sergey V.

AU - Davydova, Julia

N1 - 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.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - Ad5

KW - Ad6

KW - Adenovirus

KW - Immunother-apy

KW - Kupffer cells

KW - Liver tropism

KW - Oncolytic viruses

KW - Serotype 6

KW - Vaccine

KW - Virotherapy

UR - http://www.scopus.com/inward/record.url?scp=85117318426&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/98b6866f-cd53-3143-879f-ff1a118499e7/

U2 - 10.3390/pharmaceutics13101641

DO - 10.3390/pharmaceutics13101641

M3 - Review article

C2 - 34683934

AN - SCOPUS:85117318426

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 10

M1 - 1641

ER -