Tel Aviv University (TAU)- Research Group
Prof. Itai Benhar
Department of Molecular Microbiology and Biotechnology
The George S. Wise faculty of life sciences
Tel Aviv University
Prof. Itai Benhar
Building: Jack Green building of Biotechnology
Office phone: 972-3-6407511
Lab phone: 972-3-6407510
Office fax: 972-3-6405829
Tel Aviv University
Tel Aviv 69978, Israel
Antibody isolation and production
Our group has extensive expertise in Antibody Engineering and has developed many valuable tools for antibody isolation, for antibody optimization, for antibody production and for antibody application as diagnostics and therapeutics. Recent activities focus on IgG production using a bacterial expression system combined with in-vitro refolding (called "Inclonals" technology), production of recombinant fluorescent antibodies and studies of design principles of bispecific antibodies. Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at different antigens, enabling therapeutic strategies that are not possible with conventional monoclonal antibodies (mAbs). Since bispecific antibodies are regarded as promising therapeutic agents, several bispecific design modalities have been evaluated, but as most of them are small recombinant fragments, their utility is limited. Therapeutic mAbs are mostly of the IgG format, and two criteria should be met to make bispecific IgGs; one is that each heavy chain will only pair with the heavy chain of the second specificity. The second is that each heavy chain will only pair with the light chain of its own specificity. We recently presented a novel solution for the second criterion and are studying potential solutions for the first one.
Targeted drug-carrying phage nanomedicines
M13 filamentous bacteriophages (phages) comprise a family of bacterial viruses that grow in the bacterium E. coli. 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 10000 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 Prof. Nir Oshrov from the Medical School.
Targeted drug-carrying phage nanoparticle: general scheme
Luria Y. Raichlin D. Benhar I. (2012) Fluorescent IgG fusion proteins made in E. coli. MAbs. 1;4(3). [Epub ahead of print]
Vaks L. Benhar I. (2011) In vivo characteristics of targeted drug-carrying filamentous bacteriophage nanomedicines. J Nanobiotechnology. 20;9:58.
Hakim R. Benhar I. (2009) "Inclonals": IgGs and IgG-enzyme fusion proteins produced in an E. coli expression-refolding system. MAbs. 1(3):281-287.
Yacoby I. Benhar I. (2008) Potential of Antibacterial Nanomedicines. Nanomedicine 3(3):329-341.
Bar H. Yacoby I. Benhar I. (2008) Killing cancer cells by targeted drug-carrying phage nanomedicines. BMC Biotech. 8:37.
Yacoby I. Benhar I. (2008) Targeted Bacteriophages as Therapeutic Agents. Expert Opin Drug Targets. 5(3):321-329.
Yacoby I. Bar H. 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. Benhar I. (2006) Targeting anti bacterial agents by drug-carrying filamentous bacteriophages. Antimicrob. Agents & Chemother. 50(6):2087-2097.
Tel Aviv University (TAU)
Ben-Gurion University of the Negev (BGU)
The Hebrew University of Jerusalem (HUJI)
Bar-Ilan University (BIU)