Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Generation and characterization of E1/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII.

J L Andrews1, M J Kadan, M I Gorziglia

  • 1Genetic Therapy, Inc. (A Novartis Company), 9 West Watkins Mill Road, Gaithersburg, Maryland 20878, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|March 29, 2001
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Do school-based prevention programs impact co-occurring alcohol use and psychological distress during adolescence?

Psychological medicine·2024
Same author

Across the multiverse: exploring a diverse set of specifications related to cross-sectional and prospective associations between adolescent alcohol use and emotional problems.

Psychological medicine·2024
Same author

Investigation of Head Kinematics and Brain Strain Response During Soccer Heading Using a Custom-Fit Instrumented Mouthguard.

Annals of biomedical engineering·2024
Same author

The effect of social preference on academic diligence in adolescence.

Royal Society open science·2019
Same author

SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model.

Journal of applied microbiology·2017
Same author

Direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection: Interferon free is now.

Clinical pharmacology and therapeutics·2015
Same journal

Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
Same journal

Nox1/4 inhibitor Setanaxib treatment ameliorates cardiac function in mouse models of Duchenne Muscular Dystrophy.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
Same journal

HSP90α-USP7-DNMT1 Axis Drives Hepatocellular Carcinoma Recurrence After Microwave Ablation by Disrupting ACSS3-Mediated Propionate Metabolism.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
Same journal

Cell-penetrating asymmetric siRNA targeting MyD88 suppresses inflammasome-driven ocular degeneration and angiogenesis.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
Same journal

Targeting vaccine fusion proteins to APCs increases immunogenicity of adenoviral and mRNA-LNP vaccines.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
Same journal

Discovery of circadian clock activators with anti-obesity efficacy via suppression of adipocyte development and hypertrophy.

Molecular therapy : the journal of the American Society of Gene Therapy·2026
See all related articles

Fourth-generation adenoviral vectors show reduced toxicity in gene therapy. While highly attenuated vectors decreased liver toxicity, they also shortened the duration of therapeutic gene expression in hemophilia models.

Area of Science:

  • Gene Therapy
  • Virology
  • Immunology

Background:

  • Adenoviral vectors are crucial for gene therapy but face limitations due to host immune responses and toxicity.
  • Attenuating viral gene expression is a strategy to mitigate these challenges.

Purpose of the Study:

  • To develop and evaluate highly attenuated, fourth-generation adenoviral vectors (Av4) for gene therapy.
  • To compare the immunogenicity, toxicity, and efficacy of Av4 vectors against a third-generation vector in a hemophilia mouse model.

Main Methods:

  • Generated two fourth-generation (Av4) E1/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII (FVIII).
  • One Av4 vector (Av4DeltaE4FVIII) lacked the entire E4 region; the other (Av4orf3FVIII) retained E4 open reading frame 3.
  • Compared these vectors with a third-generation vector (Av3H8101) in vitro and in vivo in hemophiliac mice.

Related Experiment Videos

Main Results:

  • All vectors expressed functional FVIII in vitro.
  • Av4DeltaE4FVIII could not be scaled for in vivo studies.
  • Av4orf3FVIII showed significantly reduced hepatotoxicity compared to Av3H8101.
  • While initially similar, FVIII expression persisted longer with Av3H8101 than with Av4orf3FVIII at 3 months.

Conclusions:

  • Further attenuation of adenoviral vectors by removing most of the E4 region significantly reduces toxicity.
  • This enhanced attenuation comes at the cost of reduced duration of transgene expression.
  • Balancing vector safety and therapeutic efficacy remains critical in adenoviral gene therapy development.