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Monoclonal antibodies have emerged as the most successful class of biological therapeutics, providing excellent efficacy and safety profiles. Scores have been approved for use in human and hundreds more are currently in clinical trials for a broad range of indications. Monoclonal antibodies give scientists the ability to marshal the immune system against target molecules, cells or pathogens.

Transgenic mice have become a preferred means to generate fully-human monoclonal therapeutics. First-generation versions of such mice were, however, limited because they expressed only a fraction of the normal human antibody diversity. TRIANNI used advanced DNA synthesis and other techniques to overcome these limitations and create a powerful, easily accessible next-generation drug discovery resource.

The Trianni Mouse

Genetically engineered mice now act as robust engines for the generation of diverse repertoires of affinity-matured, fully-human variable regions with intrinsic drug-like properties necessary for successful development including high potency, specificity, manufacturability, solubility and low risk of immunogenicity. Few existing or contemplated human transgenic mouse platforms express a full 
human antibody repertoire. The Trianni Mouse is the only one to do so in a single organism.

THE TRIANNI MOUSE DIFFERENCE
The V gene segments in the Trianni Mouse are chimeric. However, the V regions of the antibodies that the mouse synthesizes are entirely human.

THE RESULT:
Antibodies that are optimized for function in the mouse yet express a full repertoire of human variable domains.

In the Trianni platform, transgenic mice are generated via replacement of the endogenous V, D and J segments by antibody genes that are fully optimized for function in the mouse while expressing a complete repertoire of human variable domains. Highly engineered H, K and L loci are chemically synthesized and precisely integrated into native chromosomal locations. The resulting transgenic mice possess the same antibody repertoire as humans yet produce wild-type mouse antibody responses to target antigens.

Heavy Chain CDR3 Compositions

CDR-H3 residue utilization in antibodies derived from human samples and the Trianni transgenic IgMouse. In the naive Trianni Mouse, heavy chain CDR3 (CDR-H3) aa utilization frequency is effectively the same as in humans.

Core Alleles

  • Endogenous V, D and J gene segments deleted and positionally substituted with optimized cassette
  • Chimeric gene segments (human exons paired with mouse regulatory regions)
  • Chimeric antibodies (human Vs with mouse Cs)
  • Precise genetic integration enables rapid production of next-gen variants

Key Advantages

  • Engineered versions of all three antibody genetic loci – Heavy, Kappa and Lambda
  • Novel chimeric antibody gene segments, each comprised of human coding sequences combined with mouse regulatory genomic sequences
  • Expression of a full repertoire of human heavy- and light-chain variable domains
  • Multiple enhancements to antibody gene segments
  • Retention of all mouse constant domains
  • Two light chain loci capable of expressing both Kappa and Lambda light chains
  • Normal genomic rearrangement in developing B cells leading to normal B cell development
  • Normal immune responses
  • Robust somatic hypermutation and class switching

Learn More

Download our Technical Overview for more details regarding The Trianni Mouse, including valuation studies and platforms in the TRIANNI technology pipeline.