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Publication Number
US-11618029-B2
Publication Date
2023-04-04
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 digital to biological system receives encoded biological sequence information from a remote transmitting unit and automatically activates an assembly unit to synthesize a functional biological entity. The system includes a receiving unit and software programming instructions that direct steps in the assembly unit, and after the method is initiated, no human intervention occurs until the synthesis is completed.
The assembly unit comprises or is connected to vessels containing a plurality of oligonucleotide molecules and components that transport reagents within the system. The method performs multi-level biological assembly in distinct reaction zones on a reaction container, including automated joining of oligonucleotides to assemble one or more dsDNA molecules. The software directs reagent transport from one reaction zone to the next, with a robotic arm configured to transfer oligonucleotide molecules between zones.
In the reaction container, 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. The disclosure further describes downstream production of vaccine-relevant products by directing transcription DNA to RNA and translation RNA to protein or peptide, and producing viral antigens, virus particles, or virus-like particles.
Claims Coverage
Independent claim clm-00001 covers one inventive feature: an automated, software-directed system for synthesizing double-stranded DNA molecules from provided biological sequence information with fully automated reaction-zone processing and no human intervention after initiation.
Automated dsDNA synthesis with no human intervention after initiation
An assembly unit that assembles one or more double-stranded DNA molecules according to provided biological sequence information using automated steps, wherein no human intervention occurs after the method is initiated and until the double-stranded DNA molecule is synthesized.
Vessels and transport components for automated oligonucleotide processing
The assembly unit comprises or is connected to vessels containing a plurality of oligonucleotide molecules and components that transport reagents within the system and executes automated steps for synthesizing the double-stranded DNA molecule.
Software-directed multi-zone assembly with PCR and error correction
Non-transitory computer readable medium with software programming instructions that 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, a step of DNA assembly in a third reaction zone, and directs transport of reagents from one reaction zone to the next.
Reaction plate reaction zones with robotic arm transfer
A reaction container as a reaction plate with one or more reaction wells constituting the reaction zones, and a robotic arm configured to transfer oligonucleotide molecules from the first reaction zone to the second reaction zone and from the second reaction zone to the third reaction zone, with oligonucleotide molecules successively accumulating in each reaction zone.
The independent claim is centered on a fully automated dsDNA synthesis system driven by biological sequence information and software instructions, including PCR amplification, an error correction step, and DNA assembly across separate reaction zones on a reaction plate, with robotic transfer and transport of reagents, and with no human intervention after initiation.
Stated Advantages
Rapid, locale-specific vaccine/biothreat response [as stated in the partial-content summary].
Documented Applications
Production of vaccine-relevant products including viral antigens, virus particles, and virus-like particles [as described in the partial-content summary].
Example workflows for influenza HA/NA DNA constructs and a phage PhiX genome [as described in the partial-content summary].
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