Prof. Benhar Itai

  
Affiliation:Biotechnology, The George S.Wise faculty of life sciences
Jack Green building
room 202
Tel:  (972)-3-6407511
(972)-3-6407510
 
Fax: (972)-3-6405829
 
Email: benhar@tau.ac.il
 
Personal Website:

 
Postal Address:Biotechnology
The George S.Wise faculty of life sciences

Tel Aviv University
Tel Aviv 69978

Research Interest

Targeted drug-carrying phage nanoparticles
Bacteriophages (phages) have been used for over a century for (un-orthodox) therapy of bacterial infections (also known as “phage therapy”), for nearly half a century as tools in genetic research, for nearly two decades as tools for discovery of specific target-binding proteins (mainly antibodies and peptides, known as “phage display”), for nearly a decade as tools for vaccination or as gene delivery vehicles and very recently as tools for assembly of electronic materials by nanofabrication.
Filamentous phages (Inovirus) comprise a family of bacterial viruses that have only about 10 genes and grow in well-characterized hosts, the Gram-negative bacteria. Structurally, the filamentous phage is a particle of nanometer dimensions comprising a sheath of several thousand identical alpha-helical coat proteins in a helical array that during phage maturation, self-assemble around a single-stranded circular DNA molecule at the core. A few minor proteins cap the particle at each end.
We present a novel technology related to the field of targeted drug delivery in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated phages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand (target-specific peptide, recombinant antibody or other target-specifying entity) on their surface. The drugs are chemically conjugated to the bacteriophages through labile linkages that are subject to controlled cleavage. In the conjugated state the drug is kept in an inactive prodrug state and is released and concomitantly re-activated at the target. As such, the drug-carrying phage nanoparticles may be useful as targeted drug delivery vessels for the treatment of various pathological conditions.
The targeted drug carrying phage nanoparticles have a large drug-carrying capacity in excess of 104 drug molecules/target site. We have provided POC of this approach toward the elimination of pathogenic bacteria cancer cells in closed culture systems and are now evaluating the potential of the approach in small animal disease models. In 2010 we initiated a study of targeting the pathogenic fungus, Aspergillus fumigatus using our approach which is carried out in collaboration with Dr. Nir Oshrov from the Medical School.

 

Targeted drug-carrying phage nanoparticle: general scheme

Selected Publications


  • Yacoby, I. and Benhar, I. (2008) Potential of Antibacterial Nanomedicines. Nanomedicine 3(3):329-41.
  • Bar, H., Yacoby, I. and Benhar, I. (2008) Killing cancer cells by targeted drug-carrying phage nanomedicines. BMC Biotech. 8:37.
  • Yacoby, I. and Benhar, I. (2008) Targeted Bacteriophages as Therapeutic Agents. Expert Opin Drug Targets. 5(3):321-329.
  • Yacoby, I. and Benhar, I. (2007) Targeted anti bacterial therapy. Infectious Diseases Drug Targets. 7(3):221-9.
  • Yacoby, I., Bar, H. and Benhar I. (2007) Targeted drug-carrying bacteriophages as anti bacterial nanomedicines. Antimicrob Agents Chemother. 51(6):2156-63.
  • Yacoby Y., Shamis, M., Bar, H., Shabat, D. and Benhar, I. (2006) Targeting anti bacterial agents by drug-carrying filamentous bacteriophages. Antimicrob. Agents & Chemother. 50(6):2087-2097.