platform
Allozyne technology centers on methods to incorporate amino acid analogs at specific sites into proteins using fermentation based manufacturing. These amino acid analogs possess unique chemical functions that provide proteins with novel properties not found in nature. Principal among these novel properties is the ability to readily attach chemical moieties at specific sites in the proteins. The analogs unlock an advanced class of chemical reactions that are superior to conventional methods available for protein modification.
A key aspect of the Allozyne platform is access to a sophisticated suite of computational protein design tools through its relationship with CalTech. These tools afford a close up view of the precise 3 dimensional structure of the proteins, enabling the optimal placement of amino acid analogs in the target proteins. Computational design is also a key element in the design of the tools that form the basis of one method for introducing amino acid analogs into proteins.
The methods for introducing amino acid analogs into proteins use two distinct, yet overlapping approaches. The core platform, termed substitution, is the simplest, most fundamental approach to introducing an amino acid analog. Substitution relies on manufacturing proteins in cell lines that are unable to provide one of the twenty amino acids that cells require to survive. Such cells are grown by supplying the missing amino acid. An analog is simply substituted for the natural amino acid during protein manufacture and the analog is incorporated into the protein in place of its natural counterpart.
The second method, termed mutant synthetase, relies on the engineering of the manufacturing host cell line with a mutant aminoacyl-tRNA synthetase. This modified enzyme introduces an amino acid analog into the protein translational apparatus of the cell and enables the use of a unique repertoire of analogs. The mutant synthetase method may be employed in the substitution platform, or independently, depending on the particular amino acid analog of choice.
The Allozyne platform combines these technical components to create therapeutic proteins with desirable properties. The amino acid analogs provide sites for protein modification, and may also provide other novel functional behavior to a protein that would be otherwise unavailable with the twenty amino acids found in nature. Examples of protein modifications enabled by the Allozyne platform that are of special interest in the field of protein therapeutics include bioconjugation of:
- Polyethylene glycol (PEG) or other biopolymers that enhance in vivo potency
- Peptides such as hormones, chemokines, and regulators of metabolism
- Oligosaccharides and sugars
- Toxins and drugs, for targeting to disease sites, such as cancer
Allozyne is currently focusing its efforts on three general categories of proteins that are manufactured in bacterial fermentation, including:
- Cytokines, such as IFN beta
- Single chain antibody fragments
- Fusion proteins of high potency small peptide mediators