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SELECTBIO Conferences Genome Engineering


Designer Recombinases for Therapeutic Genome Engineering

Frank Buchholz, Professor, University of Technology Dresden

Genome editing tools are currently revolutionizing biomedical research and promise to allow precision medicine for future therapies. Site specific recombinases (SSRs) were among early genome engineering tools that have found wide-spread use in the research community. SSRs can be expressed in model organisms without causing detrimental effects while efficiently and specifically modifying the genome. However, their inflexibility to recombine predefined target sequences has hampered the translation of SSRs into clinical applications. We have developed an efficient directed molecular evolution approach, coupled with rational design to change the DNA binding specificity of Cre recombinase. Possible therapeutic applications for this technology will be discussed. In particular, I will present data on the generation of a third generation broad-range recombinase (Brec1) that site-specifically recognizes a 34 bp sequence present in long terminal repeats (LTRs) of the majority of HIV-1 strains and subtypes. Brec1 efficiently, precisely and safely removes the integrated provirus from infected cells. Moreover, Brec1 acts efficaciously on clinical HIV-1 isolates in vitro and in vivo, particularly in humanized mice “personalized” with patient-derived cells. Thus, Brec1 represents a novel and potent antiviral reagent with a broad clinical application in the context of future curative HIV-1 therapy strategies.

Add to Calendar ▼2015-10-07 00:00:002015-10-08 00:00:00Europe/LondonGenome EngineeringGenome Engineering in Hanover, GermanyHanover,