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
Editorial
. 2022 Mar 23:28:168-174.
doi: 10.1016/j.omtn.2022.03.002. eCollection 2022 Jun 14.

Editorial: In vitro mechanistic evaluation of nucleic acid polymers: A cautionary tale

Affiliations
Editorial

Editorial: In vitro mechanistic evaluation of nucleic acid polymers: A cautionary tale

Andrew Vaillant. Mol Ther Nucleic Acids. .
No abstract available

Keywords: hepatitis B; mechanism of action; nucleic acid polymer; oligonucleotide; transfection artifacts.

PubMed Disclaimer

Conflict of interest statement

A.V. is an employee and shareholder of Replicor Inc.

Figures

None
Graphical abstract
Figure 1
Figure 1
Sequence and chemical modifications of various NAPs. All NAPs contain phosphorothioate at each linkage
Figure 2
Figure 2
Effects of pH on NAP structure and antiviral activity against HBV in vitro with and without transfection and in vivo
Figure 3
Figure 3
NAP trafficking and effects on antiviral activity (A) Comparison of oligonucleotide trafficking occurring in vivo and in humans with that occurring in vitro. (B) Artifacts associated with transfection-based approaches with NAPs.
Figure 4
Figure 4
pH can influence the secondary structure of NAPs (A) Secondary structure of NAPs with various sequence compositions under non-denaturing and denaturing gel electrophoresis. (B) Effect of pH on the secondary structure of REP 2107. All NAPs contain phosphorothioate at each linkage. A, adenosine; G, guanosine; T, thymidine; C, cytidine; d, deoxyribose (DNA); 2′OMe, 2′O-methyl-modified ribose (RNA).
Figure 5
Figure 5
Model for the impact of LNA modification on the antiviral interactions of NAPs Hydrophilic regions of target alpha helices for NAPs are indicated in blue and hydrophobic regions in red. Hydrophobic interactions and their relative strength are indicated by arrows.

References

    1. Vaillant A. Nucleic acid polymers: broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection. Antivir. Res. 2016;133:32–40. - PubMed
    1. Vaillant A. Rep 2139: antiviral mechanisms and applications in achieving functional control of HBV and HDV infection. ACS Infect Dis. 2019;5:675–687. - PubMed
    1. Bazinet M., Pantea V., Placinta G., Moscalu I., Cebotarescu V., Cojuhari L., Jimbei P., Iarovoi L., Smesnoi V., Musteata T., et al. Safety and efficacy of 48 Weeks REP 2139 or REP 2165, tenofovir disoproxil, and pegylated interferon alfa-2a in patients with chronic HBV infection naive to nucleos(t)ide therapy. Gastroenterology. 2020;158:2180–2194. - PubMed
    1. Bazinet M., Pantea V., Cebotarescu V., Cojuhari L., Jimbei P., Anderson M., Gersch J., Holzmayer V., Elsner C., Krawczyk A., et al. Persistent control of HBV and HDV infection following REP 2139-Ca and pegIFN therapy in chronic HBV/HDV co-infection. Hepatol. Commun. 2020;5:189–202. - PMC - PubMed
    1. Kao C.C., Nie Y., Ren S., Tilani N., De Costa T.S., Pamdey R.K., Hong J., Smith D.B., Symons J.,A., Beigelman L., et al. Mechanism of action of hepatitis B virus S antigen transport-inhibiting oligonucleotide polymer, STOPS, molecules. Mol. Ther. Nucleic Acids. 2021;27:335–348. - PMC - PubMed

Publication types