Synthetic genome
Inventors
FREDENS, Julius • Wang, Kaihang • DE LA TORRE, Daniel • FUNKE, Louise F. H. • Robertson, Wesley E. • Chin, Jason W.
Assignees
United Kingdom Research and Innovation • Scarab Genomics LLC
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Publication Number
US-12378547-B2
Publication Date
2025-08-05
Expiration Date
Abstract
The current invention provides a synthetic prokaryotic genome comprising 5 or fewer occurrences of one or more sense codons; and/or a synthetic prokaryotic genome derived from a parent genome, wherein the synthetic prokaryotic genome comprises less than 10%, 5%, 2%, 1%, 0.5%, 0.1% of the occurrences of one or more sense codons, relative to the parent genome; and/or a synthetic prokaryotic genome comprising 100 or more, 200 or more, or 1000 or more genes with no occurrences of one or more sense codons.
Core Innovation
The invention is directed to a synthetic E. coli genome in which occurrences of an amber stop codon (TAG) are replaced with TAA and occurrences of serine codons are replaced with synonymous codons. The recoding is defined by occurrence replacement thresholds for TAG-to-TAA substitution and for serine-codon replacement with synonymous codons.
The disclosed concept is supported by a synthetic, genome-wide recoded E. coli implementation (Syn61) that provides evidence for genome-wide TAG/TCA/TCG recoding and practical viability/performance outcomes. The described recoding is evaluated for design flaws and functional consequences, including effects related to synonymous codon compression and elimination of target-codon decoding tRNAs/release factor dependencies.
Claims Coverage
The independent claim set includes four independently defined recoding percentage levels (90%, 95%, 99%, and 100%) for TAG-to-TAA replacement and for serine-codon replacement with synonymous codons. Across the independents, the coverage focuses on two coordinated inventive features: TAG-to-TAA occurrence replacement and serine synonymous-codon occurrence replacement, each expressed as threshold percentages.
High-percentage TAG-to-TAA recoding with synonymous serine-codon replacement
A synthetic E. coli genome, wherein 90% or more of occurrences of an amber stop codon (TAG) are replaced with TAA and 90% or more of occurrences of a serine codon are replaced with a synonymous codon.
Higher-percentage TAG-to-TAA recoding with synonymous serine-codon replacement
A synthetic E. coli genome, wherein 95% or more of occurrences of an amber stop codon (TAG) are replaced with TAA and 95% or more of occurrences of a serine codon are replaced with a synonymous codon.
Substantially complete TAG-to-TAA recoding with synonymous serine-codon replacement
A synthetic E. coli genome, wherein 99% or more of occurrences of an amber stop codon (TAG) are replaced with TAA and 99% or more of occurrences of a serine codon are replaced with a synonymous codon.
Complete TAG-to-TAA recoding with complete synonymous serine-codon replacement
A synthetic E. coli genome, wherein 100% of occurrences of an amber stop codon (TAG) are replaced with TAA and 100% of occurrences of a serine codon are replaced with a synonymous codon.
Overall, the claim coverage is the engineered replacement of amber stop codon (TAG) occurrences with TAA and the replacement of serine codon occurrences with synonymous codons, with independent claims specifying progressively higher occurrence replacement thresholds up to complete (100%) replacement.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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