Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 28;22(5):2417.
doi: 10.3390/ijms22052417.

Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors

Florian Kreppel  1 , Claudia Hagedorn  1
Affiliations
Review

Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors

Florian Kreppel et al. Int J Mol Sci. .

Abstract

Adenovirus-based gene transfer vectors are the most frequently used vector type in gene therapy clinical trials to date, and they play an important role as genetic vaccine candidates during the ongoing SARS-CoV-2 pandemic. Immediately upon delivery, adenovirus-based vectors exhibit multiple complex vector-host interactions and induce innate and adaptive immune responses. This can severely limit their safety and efficacy, particularly after delivery through the blood stream. In this review article we summarize two strategies to modulate Ad vector-induced immune responses: extensive genomic and chemical capsid modifications. Both strategies have shown beneficial effects in a number of preclinical studies while potential synergistic effects warrant further investigations.

Keywords: HPMA; PEGylation; adenovirus; cloaking; immune response; shielding; stealthing; vector.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Reddy V.S., Natchiar S.K., Stewart P.L., Nemerow G.R. Crystal structure of human adenovirus at 3.5 A resolution. Science. 2010;329:1071–1075. doi: 10.1126/science.1187292. - DOI - PMC - PubMed
    1. Liu H., Jin L., Koh S.B.S., Atanasov I., Schein S., Wu L. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science. 2010;329:1038–1043. doi: 10.1126/science.1187433. - DOI - PMC - PubMed
    1. Pearson S., Jia H., Kandachi K. China approves first gene therapy. Nat. Biotechnol. 2004;22:3–4. doi: 10.1038/nbt0104-3. - DOI - PMC - PubMed
    1. Yang Y., Nunes F.A., Berencsi K., Furth E.E., Gönczöl E., Wilson J.M. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. USA. 1994;91:4407–4411. doi: 10.1073/pnas.91.10.4407. - DOI - PMC - PubMed
    1. Yang Y., Ertl H.C., Wilson J.M. MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. Immunity. 1994;1:433–442. doi: 10.1016/1074-7613(94)90074-4. - DOI - PubMed

LinkOut - more resources