Cambridge University seeks to license cell-free display technology

Seeking Partnership, Licensing

Researchers at the University of Cambridge are seeking commercial partners for licensing, collaboration and development of their patented cell-free display technology used for developing novel therapeutics.

Dr Florian Hollfelder and his colleagues in the Department of Biochemistry at the University of Cambridge have developed a new method of displaying selectable polypeptides. The method involves covalently linking polypeptides to their coding nucleic acid via a covalent bond between alkyl guanine transferase (AGT), expressed as a protein fused to the polypeptide, and its substrate linked to the DNA.

This method has the potential to allow for efficient screening of large numbers of displayed polypeptides using larger library sizes than permitted by existing techniques and in diverse reaction conditions and also enables screening of proteins that are toxic to cells or with impaired translocation.

Commercialisation and patent status

We are seeking commercial partners for licensing, collaboration and development of this technology. This technology is protected by the UK patent application number GB0714698.8 filed on 27/07/2007.

Potential Uses:

• Directed evolution of functional proteins by linking protein behaviour to coding DNA
• Cell-free display of large DNA libraries up to 1010
• Selection & affinity maturation of protein binders
• Use to develop protein therapeutics
• Screening of proteins that are toxic to cells or are translocated inefficiently

Advantages:

• Simple, efficient method for the stable linkage of genotype with phenotype via a covalent bond
• Accurate coupling of protein to coding DNA by in vitro compartmentalisation of templates
• Advantages of an in vitro system:
• a greater variety of proteins can be expressed
• library not limited by transformation efficiency
• freedom to govern selection conditions
• potential to include non-natural amino acids
• Easy to implement in the laboratory
• The multivalent system increases:
• efficiency of nucleic acid-protein conjugate formation
• diversity of selected conjugates including those with weak binding, to evolve peptides with improved binding features
• enrichment that may accelerate directed evolution

Background

Current display techniques have limitations and are not easily deployable in different formats. In vivo selections are limited by factors including low transformation efficiency and cellular selection conditions. Phage display, arguably the most widely used technique to generate protein binders, is limited by in vivo protein expression. Several in vitro approaches have been developed, however these are limited by factors including non-covalent linkages between DNA and protein or less stable RNA templates.

A simple in vitro polypeptide display method that covalently links a polypeptide to its encoding DNA is needed that offers advantages in the display and selection of polypeptides compared with existing methods.