Related Experiment Video

Updated: Aug 5, 2026

Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
13:36

Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches

Published on: May 6, 2015

Signaling antibodies complexed with adenovirus circumvent CAR and integrin interactions and improve gene delivery

E Li1, S L Brown, D J Von Seggern

  • 1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Gene Therapy
|October 6, 2000
PubMed

Insights

Researchers developed a novel gene delivery method using bifunctional antibodies to target adenoviral vectors. This approach enhances gene transfer efficiency by leveraging cell signaling pathways, overcoming limitations of current receptor-dependent methods.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Gene Therapy

Background:

  • Adenoviral (Ad) vectors are widely used for gene delivery but face limitations.
  • Current Ad vectors target the coxsackie adenovirus receptor (CAR), which is broadly distributed.
  • Some cell types lack CAR or other internalization receptors, hindering Ad-mediated gene delivery.

Purpose of the Study:

  • To develop a novel vector targeting approach for Ad-mediated gene delivery.
  • To overcome limitations of CAR-dependent targeting and improve gene delivery to resistant cell types.
  • To enhance the selectivity and efficiency of gene transfer using Ad vectors.

Main Methods:

  • Developed bifunctional monoclonal antibodies (mAbs) by fusing recombinant growth factors/cytokines (TNF-alpha, IGF-1, EGF) to an antibody targeting the viral penton base.
  • These growth factors/cytokines trigger phosphatidylinositol-3-OH kinase (PI3K) activation, a key signaling pathway for Ad internalization.
  • Complexed Ad vectors with bifunctional mAbs and tested gene delivery to human melanoma cells lacking alphav integrins and using fiberless Ad particles.

Main Results:

  • Gene delivery increased 10 to 50-fold to human melanoma cells lacking alphav integrins when using Ad vectors complexed with bifunctional mAbs.
  • Enhanced gene delivery was observed with fiberless adenovirus particles, which do not bind to CAR.
  • Improved gene delivery correlated with increased virus internalization, attachment, and PI3K activity.

Conclusions:

  • Bifunctional mAbs targeting cell signaling pathways offer a novel strategy for Ad vector targeting.
  • This approach effectively bypasses normal Ad receptors (CAR and alphav integrins) for gene delivery.
  • The method holds potential for widespread application in enhancing gene transfer selectivity and efficiency.

More Related Videos

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System11:06

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting08:14

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

Published on: October 26, 2018

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...