Stem cells and biobanks Technology Offers Page 8

RAMOT at Tel Aviv University Ltd. posted this:

We have demonstrated a proof of principle for sensitization of a laboratory strain of E. coli to streptomycin and to nalidixic acid using a lambda phage as a gene delivery vehicle. The phage infects E. coli and transfers genes conferring dominant sensitivity to antibiotics (rpsL and gyrA). The infected bacteria are favored in the environmental settings due to the presence of a resistance gene to a disinfectant agent, tellurite, in the phage genome (1). Short term commercialization plans (2-3 years): • Show that the lambda phage is effectively lysogenizing bacteria on environmental surfaces, not only in solutions or petri dishes. • Adapt the lambda phage to an E. coli pathogenic host by repeated selection cycles. • Alternatively, transfer the sensitization cassette to another phage. • Test the efficiency of the delivery vehicle to enrich the drug-sensitive pathogen population in mice cages, which will be sprayed with pathogens, phages and tellurite to simulate hospital settings. • Test whether mice in treated cages vs. mice in untreated cages can be cured using antibiotics to which the pathogens are resistant. • Test efficiency of use in hospital settings (Dr. Daniel T. Laish, Director of ICU in a Florida-based hospital offered to carry out the research in their facilities). • Obtain an FDA license. Long term goals (3-6 years): • Obtain temperate phage specific for different pathogens (MRSA, VRE, etc.) from different collections, or isolate new temperate phages. • Genetically engineer to harbor the cassette encoding rpsL, gyrA (conferring dominant sensitivity), and tellurite-resistance (for selection). • Test the efficiency of the delivery vehicle to enrich the drug-sensitive pathogen population in mice cages, which will be sprayed with pathogens, phages and tellurite to simulate hospital settings. • Test whether mice in treated cages vs. mice in untreated cages can be cured using antibiotics to which the pathogens are resistant. • Obtain an FDA license. Project ID : 2-2012-282

RAMOT at Tel Aviv University Ltd. posted this:

Silver exhibit antibacterial activity in either ionic or metallic forms, albeit by two different mechanisms: silver ions penetrating the bacterial cell interact with the respiratory chain and with cellular DNA. Metallic silver – mostly applied as silver nano-crystals – affects primarily cell membrane by physically 'puncturing' it or by slow release of silver ions resulting from oxidative environment. Both forms - silver nano-crystals or silver ions attached to ion exchanging polymers, mostly applied as impregnated dressings, suffer from poor migration from the supplied 'reservoir' to and into their targeted microbial biofilm. While ionic silver has poor migration due to interaction with chloride and other anions, resulting in insoluble salt precipitation, silver nano crystals migration is physically restricted. We have recently developed novel protein-silver hybrids, comprised of a biologically active glucose oxidase core, coated with a thin (~1.5nm) outer layer of metallic silver. The silver-glucose oxidase hybrid retains enzymatic activity and serves as a unique antibacterial agent, generating silver ions in situ. The soluble silver–glucose oxidase hybrid diffuses into the targeted biofilm vicinity and penetrate into its larger pores. Upon scavenging of glucose traces inside the biofilm, the glucose oxidase core of the hybrid produces hydrogen peroxide, capable of locally oxidizing and dissolving metallic silver, thus affecting enzymatically attenuated in situ silver ions release from the hybrid's silver coating into the immediate vicinity of the targeted cells, resulting in effective disinfection. Project ID : 10-2011-255