The present inventions describes a Facile Accelerated Specific Therapeutic (FAST) pipeline to rapidly design, built and test peptide nucleic acid treatments against mammalian or microbial genes of interest. The invention may include a bioinformatics application for facile and accelerated high throughput design of peptide nucleic acids (PNAs) that act as inhibitors of expression of specific targeted genes by binding to their mRNA to block translation, or PNA activators that can activate expression of target genes by binding to the respective promoter regions and recruitment of transcriptional activators. The invention may further involve automated and high throughput parallel synthesis of a PNA inhibitor/activator library for generation of on-site therapeutic molecules, which may reduce storage requirements, and the development of efficient delivery of therapeutic PNAs to host cells to overcome challenges of transport, toxicity, and bioavailability. The invention may further involve the testing of designed and built PNAs in a high throughput manner in a relevant infection, or mammalian cell culture model. The proposed invention may allow identification of important gene targets, and quickly generate translatable therapies that can be tested under host conditions, and most importantly develop a countermeasure platform that can be deployed on-site in the future to generate therapies in short time scales.

The present inventions describes a Facile Accelerated Specific Therapeutic (FAST) pipeline to rapidly design, built and test peptide nucleic acid treatments against mammalian or microbial genes of interest. The invention may include a bioinformatics application for facile and accelerated high throughput design of peptide nucleic acids (PNAs) that act as inhibitors of expression of specific targeted genes by binding to their mRNA to block translation, or PNA activators that can activate expression of target genes by binding to the respective promoter regions and recruitment of transcriptional activators. The invention may further involve automated and high throughput parallel synthesis of a PNA inhibitor/activator library for generation of on-site therapeutic molecules, which may reduce storage requirements, and the development of efficient delivery of therapeutic PNAs to host cells to overcome challenges of transport, toxicity, and bioavailability. The invention may further involve the testing of designed and built PNAs in a high throughput manner in a relevant infection, or mammalian cell culture model. The proposed invention may allow identification of important gene targets, and quickly generate translatable therapies that can be tested under host conditions, and most importantly develop a countermeasure platform that can be deployed on-site in the future to generate therapies in short time scales.

A method for searching data includes storing a probe data and a target data expressed in a first orthogonal domain. The target data includes potential probe match data each characterized by the length of the target data. The probe data representation and the target data are transformed into an orthogonal domain. In the orthogonal domain, the target data is encoded with modulation functions to produce a plurality of encoded target data, each of the modulation functions having a position index corresponding to one of the potential probe match data. The plurality of encoded target data is interfered with the probe data in the orthogonal domain and an inverse transform result is obtained. If the inverse transform result exceeds a threshold, information is output indicating a match between the probe data and a corresponding one of the potential probe match data.

The disclosure provides, inter alia, methods of determining the three-dimensional structure of a polypeptide, given a subject protein sequence, e.g., a primary amino acid sequence. The methods can efficiently determine structures, including those of de novo proteins for example, those without known homologues with pre-determined structures.

Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

The invention provides systems and methods for discovering candidate therapies for genetic conditions and also for screening those therapies in vitro for evidence of neurotoxicity. Where a medical condition is a consequence of a genetic target such as a mutated gene, the disclosure provides in silico methods to generate lists of candidate sequences for antisense oligonucleotides (ASOs) that will potentially bind to the gene or transcripts from the gene in vivo and treat the associated condition by restoring a healthy phenotype of gene expression. The invention provides in vitro methods for screening candidate ASO sequences for symptoms of neurotoxicity in vivo. For example, candidate sequences that are output by the in silico analytical pipeline can be synthesized and assayed against live cells in vitro.

A system for producing a therapeutic oligomer includes a computing device configured to design a proposed therapeutic oligomer sequence, wherein designing further comprises generating a genomic library for an organism from a gene target, initiating a sequence identification function, identifying a genomic locus that the proposed therapeutic oligomer sequence is predicted to bond to as a function of an off-target sequence function, selecting the proposed therapeutic oligomer sequence as a function of the sequence identification function, the genomic locus, and a criterion element, and synthesize a therapeutic oligomer as a function of the proposed therapeutic oligomer sequence.

A system for producing a therapeutic oligomer includes a computing device configured to design a proposed therapeutic oligomer sequence, wherein designing further comprises generating a genomic library for an organism from a gene target, initiating a sequence identification function, identifying a genomic locus that the proposed therapeutic oligomer sequence is predicted to bond to as a function of an off-target sequence function, selecting the proposed therapeutic oligomer sequence as a function of the sequence identification function, the genomic locus, and a criterion element, and synthesize a therapeutic oligomer as a function of the proposed therapeutic oligomer sequence.

The present disclosure relates to in vitro experiments and in silico computation and machine-learning based techniques to iteratively improve a process for identifying binders that can bind any given molecular target. Particularly, aspects of the present disclosure are directed to obtaining sequence data for aptamers that bind to a target, where the sequence data has a first signal to noise ratio, generating, by a search process, a first set of aptamer sequences derived from the sequence data, obtaining subsequent sequence data for subsequent aptamers that bind to the target, where the subsequent aptamers includes aptamers synthesized from the first set of aptamer sequences, and the subsequent sequence data has a second signal to noise ratio greater than the first signal to noise ratio, generating, by a linear machine-learning model, a second set of aptamer sequences derived from the subsequent sequence data, and outputting the second set of aptamer sequences.