Biociphering™ Platform

We have developed and optimized two distinct proprietary Biociphering™ platforms that enable site-specific incorporation of non-natural amino acids anywhere along the amino acid sequence of the target protein. These proprietary Biociphering™ technologies allow for key modifications to be made to the cellular machinery involved in protein synthesis. The non-natural amino acids utilized contain moieties that allow for a multitude of bioconjugates to be attached. By carefully selecting a conjugate and site of attachment, the therapeutic properties of virtually any protein can be enhanced.

CAESAR

The CAESAR biociphering platform is based on manufacturing proteins in E. coli bacteria. Allozyne has engineered a strain of E. coli that cannot produce a naturally occurring amino acid called methionine. When a target protein is grown in this strain, a non-natural amino acid is substituted in place of methionine along the protein sequence. The non-natural amino acid comes with a chemical hinge which can now serve as a site for attachment of a bioconjugate. The chemistry tools that are used to attach the bioconjugate are specific to the non-natural amino acid chemical hinge and have no effect on other parts of amino acid sequence of the protein.

Historical origin of the Caesar cipher.

VIGENÈRE

The VIGENÈRE biociphering platform is based on manufacturing proteins in mammalian cells. Allozyne has engineered a specific strain of mammalian cells that can produce a modified version of the cellular machinery required for manufacturing proteins. This machinery is able to utilize specific sites for insertion of the non-natural amino acid anywhere along the protein sequence. The non-natural amino acid comes with a chemical hinge which can now serve as a site for attachment of a bioconjugate. The chemistry tools that are used to attach the bioconjugate are specific to the non-natural amino acid chemical hinge and have no effect on other parts of amino acid sequence of the protein.

Historical origin of the Vigenère cipher.

Technical differences between CAESAR and VIGENÈRE.

ALLOZYNE has enabled its biociphering platforms to create a host of distinct product opportunities in the autoimmunity and oncology markets. ALLOZYNE’s biociphering platforms have led to the development of a robust pipeline focused to treat unmet medical needs for various autoimmune diseases as well as oncology.

AZ01: Long acting interferon beta (IFNβ) for treatment of relapsing remitting multiple sclerosis

AZ17: Bispecific antibody for treatment of various autoimmune and inflammatory diseases, including Crohn’s disease.

AZ05: Antibody-drug conjugate for treatment of various solid tumors

In addition to our pipeline product candidates, the CAESAR and VIGENÈRE platforms also allow several other therapeutic configurations. Several of these configurations have been constructed by us.

Platform and Pipeline at ALLOZYNE
Scientific Publications

Wang A, Nairn NW, Johnson RS, Tirrell DA, Grabstein. Processing of N-terminal unnatural amino acids in recombinant human interferon-beta in Escherichia coli. Chembiochem. 2008, 9, 324 – 330.

Wang A. Therapeutic Protein Engineering via the Incorporation of Non-natural Amino Acids. Ehrlich II – 2nd World Conference on Magic Bullets Oct 3-5 2008, Nurnberg, Germany
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Nairn NW, Graddis TJ, Wang A, Shanebeck K, and Grabstein K. Site-specific PEGylation of interferon–beta by Cu(I)–catalyzed cycloaddition. 234th American Chemical Society National Meeting, 2007, Boston MA.
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Link J, Mock ML, Tirrell DA. Non-canonical amino acids in protein engineering. Current Opinion in Biotechnology. 2003, 14: 603-609.

Kiick KL, Saxon E, Tirrell DA, Bertozzi CR. Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation. Proceedings of the National Academy of Sciences. 2002, 99: 19-24.

Kiick KL, Tirrell DA. Protein engineering by in vivo incorporation of non-natural amino acids: control of incorporation of methionine analogues by methionyl-tRNA synthetase. Tetrahedron. 2000, 56: 9487-9493.

If you are interested in receiving information on these publications please email bd@allozyne.com