Evidence map›Paper›PMID 36563152›Full record

ArticleScience advances2022

An ultralong-acting tenofovir ProTide nanoformulation achieves monthslong HBV suppression.

Srijanee Das, Weimin Wang, Murali Ganesan, Franchesca Fonseca-Lanza, Denise A Cobb, Grace Bybee, Yimin Sun, Lili Guo, Brandon Hanson, Samuel M Cohen and 4 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Prospects for Controlling Hepatitis B Globally.Pathogens (Basel, Switzerland) · 2024
    Review
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Srijanee DasDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-2792-0718
Weimin WangDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Murali GanesanDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.ORCID 0000-0002-2981-568X
Franchesca Fonseca-LanzaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-2897-6131
Denise A CobbDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0003-2213-4424
Grace BybeeDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
Yimin SunDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Lili GuoDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-7374-5471
Brandon HansonDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Samuel M CohenDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-5047-0962
Howard E GendelmanDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-7831-0370
Natalia A OsnaDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.ORCID 0000-0001-7498-0556
Benson J EdagwaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0003-1484-9331
Larisa Y PoluektovaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0001-7339-8732
University of Nebraska Medical Center · USVA Nebraska Western Iowa Health Care System · US

Funding

Prodrug Formulations Create Sustained-Release AntiretroviralsR01AI145542 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Benson Edagwa, Howard E Gendelman · 2019 to 2026
$5.3M
Targeted lipid nanoparticles for gene therapeutics delivery approach to eradicating HIV reservoirsR01MH121402 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Benson Edagwa, Howard E Gendelman · 2019 to 2026
$4.9M
LASER ART for PrePR01AI158160 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI EDAGWA, BENSON, GENDELMAN, HOWARD E · 2021 to 2025
$3.5M
New generation of long acting nucleos(t)ides and immune stimulant for treatment of chronic hepatitis BR01AI163042 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Benson Edagwa, NATALIA ALEKSANDR OSNA · 2022 to 2026
$3.1M
Ethanol suppresses HBV peptide-MHC Class I presentation on hepatocytesK01AA026864 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GANESAN, MURALI · 2018 to 2022
$684k
NIAAA NIH HHS K01 AA026864NIAID NIH HHS R01 AI145542NIAID NIH HHS R01 AI158160NIAID NIH HHS R01 AI163042NIMH NIH HHS R01 MH121402
6 · The paper itself

Abstract

Treatment of chronic hepatitis B virus (HBV) requires lifelong daily therapy. However, suboptimal adherence to the existing daily therapy has led to the need for ultralong-acting antivirals. A lipophilic and hydrophobic ProTide was made by replacing the alanyl isopropyl ester present in tenofovir alafenamide (TAF) with a docosyl phenyl alanyl ester, now referred to as M1TFV. NM1TFV and nanoformulated TAF (NTAF) nanocrystals were formulated by high-pressure homogenization. A single intramuscular injection of NM1TFV, but not NTAF, delivered at a dose of TFV equivalents (168 milligrams per kilogram) demonstrated monthslong antiviral activities in both HBV-transgenic and human hepatocyte transplanted TK-NOG mice. The suppression of HBV DNA in blood was maintained for 3 months. Laboratory experiments on HBV-transfected HepG2.2.15 cells affirmed the animal results and the critical role of docosanol in the sustained NM1TFV antiviral responses. These results provide clear "proof of concept" toward an emerging therapeutic paradigm for the treatment and prevention of HBV infection.

Identifiers

PMID36563152
PMCPMC9788773
OpenAlexW4312179396

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.