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Publication Number
US-12589396-B2
Publication Date
2026-03-31
Expiration Date
Abstract
The present invention provides a system for receiving biological sequence information and activating the synthesis of a biological entity. The system has a receiving unit for receiving a signal encoding biological sequence information transmitted from a transmitting unit. The transmitting unit can be present at a remote location from the receiving unit. The system also has an assembly unit connected to the receiving unit, and the assembly unit assembles the biological entity according to the biological sequence information. Thus, according to the present invention biological sequence information can be digitally transmitted to a remote location and the information converted into a biological entity, for example a protein useful as a vaccine, immediately upon being received by the receiving unit and without further human intervention after preparing the system for receipt of the information. The invention is useful, for example, for rapidly responding to viral and other biological threats that are specific to a particular locale.
Core Innovation
The disclosure describes a system that transmits encoded biological sequence information from a remote transmitting unit to a receiving unit and uses an assembly unit to synthesize biological entities according to the received information. The assembly unit automatically assembles biological entities including DNA, RNA, protein, peptides, and virus/phage and vaccine-related products with little and/or no human intervention after setup and initiation.
The system includes software programming instructions on a non-transitory computer readable medium that direct steps in the assembly unit. The software programming instructions convert received sequence information into programmed assembly and synthesis instructions and direct a workflow implemented across reaction zones within a reaction plate, where reagents are transported from one reaction zone to the next, and the system includes robotic transfer components to move oligonucleotide molecules between reaction zones.
The disclosed automated workflow comprises assembling one or more dsDNA molecules by joining a plurality of oligonucleotides, including PCR amplification in a first reaction zone, error correction in a second reaction zone performed after the PCR amplification, and DNA assembly in a third reaction zone. The automated method is initiated and continues without human intervention until the dsDNA molecule is synthesized, using the assembly unit, reagent vessels, and automated transport and execution components directed by the software programming instructions.
The disclosure also describes downstream contexts including transcription and translation workflows, and optionally in vivo viral particle production. The system is described as supporting sequence design and post-synthesis or post-transcriptional modifications such as DNA methylation and RNA capping and modifications, and it includes kit formats and reaction-zone concepts implemented using reaction containers such as 96-well plates and robotic transfers.
Claims Coverage
The partial claim set provides one independent claim that covers an automated, no-human-intervention method and system for synthesizing dsDNA from provided biological sequence information. The claim includes five inventive features, including automated reaction-zone workflow, robotic reagent and oligonucleotide transport, and software-directed execution with specified reaction steps in sequence zones on a reaction plate.
Automated dsDNA synthesis without human intervention after initiation
The method includes assembly of one or more dsDNA molecules by joining a plurality of oligonucleotides, and no human intervention occurs after the method is initiated and until the dsDNA molecule is synthesized.
System with assembly unit and vessels for automated reactions
The method provides a system comprising an assembly unit that assembles the double-stranded DNA molecule according to the biological sequence information, vessels within or connected to the assembly unit containing a plurality of oligonucleotide molecules and reagents for performing reactions, and components that transport the reagents within the system and that execute steps in an automated method.
Software programming instructions directing automated assembly steps across reaction zones
The system comprises a non-transitory computer readable medium containing software programming instructions that direct steps in the assembly unit for assembling the plurality of oligonucleotide molecules into the dsDNA molecule in the automated method.
Reaction plate with first/second/third reaction zones for PCR, error correction, and DNA assembly
The software programming instructions direct a step of PCR amplification in a first reaction zone, a step of error correction in a second reaction zone performed after the PCR amplification, and a step of DNA assembly in a third reaction zone, and direct the transport of reagents from one reaction zone to the next, where the reaction container is a reaction plate and the reaction zones comprise one or more reaction wells.
Robotic arm transferring oligonucleotides between reaction zones
The system includes a robotic arm configured to transfer the oligonucleotide molecules from the first reaction zone to the second reaction zone, with the oligonucleotide molecules successively accumulating in each reaction zone.
Across the independent claim, coverage centers on an assembly-unit based automated dsDNA synthesis workflow driven by software programming instructions, implemented on reaction zones of a reaction plate with reagent transport and robotic transfer, including PCR amplification, error correction, and DNA assembly, performed without human intervention after initiation.
Stated Advantages
No human intervention occurs after the method is initiated and until the dsDNA molecule is synthesized.
Documented Applications
Automated assembly of influenza HA/NA DNA constructs.
Generation of phage PhiX genomes via overlapping fragments and automated assembly/amplification steps.
Proof-of-concept immunological response using self-amplifying RNA vaccine constructs.
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