The disclosure provides genetically engineered microorganisms capable of producing antigen-binding molecules. Additionally, the disclosure provides engineered microorganisms comprising one or more disrupted genes to strategically divert carbon flux away from undesirable products towards products, and optionally co-products, of interest. Further, the disclosure enables co-production of useful chemicals from gaseous substrates.

Disclosed herein are compositions comprising one or more therapeutic proteins for oral administration. The disclosed proteins, which may be directed to a variety of GI and systemic target antigens, resist denaturation and degradation in the stomach and intestines of a patient. The disclosed proteins may be delivered intact to a target region within the gut, or anywhere in body to target specific molecules, cells, tissues, or organs. In some embodiments, the disclosed proteins may include two or more proteins for targeting two or more target antigens.

Disclosed herein are compositions comprising one or more therapeutic proteins for oral administration. The disclosed proteins, which may be directed to a variety of GI and systemic target antigens, resist denaturation and degradation in the stomach and intestines of a patient. The disclosed proteins may be delivered intact to a target region within the gut, or anywhere in body to target specific molecules, cells, tissues, or organs. In some embodiments, the disclosed proteins may include two or more proteins for targeting two or more target antigens.

RNA-guided programmable cytosine and adenine base editors are a powerful class of genome editing tool for the introduction of localized base transitions without generating a double-stranded DNA break. Base editors (BE) have an optimal window of activity relative to the PAM recognized by the Cas9 enzyme and these constructs are strand selective. Here we demonstrate that fusion of a programmable DNA-binding domain (pDBD) or another Cas9 orthologue to spCas9-BE, we can produce an RNA-programmable Cas9-BE-pDBD chimera or Cas9-BE-Cas9 chimeras with dramatically improved activities and increased targeting range. Cas9-pDBD or Cas9-Cas9 fusion base editors display an expanded targeting repertoire and achieve highly specific genome editing, which can be tailored to achieve extremely precise genome editing at nearly any genomic locus.

RNA-guided programmable cytosine and adenine base editors are a powerful class of genome editing tool for the introduction of localized base transitions without generating a double-stranded DNA break. Base editors (BE) have an optimal window of activity relative to the PAM recognized by the Cas9 enzyme and these constructs are strand selective. Here we demonstrate that fusion of a programmable DNA-binding domain (pDBD) or another Cas9 orthologue to spCas9-BE, we can produce an RNA-programmable Cas9-BE-pDBD chimera or Cas9-BE-Cas9 chimeras with dramatically improved activities and increased targeting range. Cas9-pDBD or Cas9-Cas9 fusion base editors display an expanded targeting repertoire and achieve highly specific genome editing, which can be tailored to achieve extremely precise genome editing at nearly any genomic locus.

The present disclosure relates to systems, compositions and methods for modifying target nucleic acid sequences.

The present disclosure relates to systems, compositions and methods for modifying target nucleic acid sequences.

A protein scaffold includes a plurality of EutM subunits and a multi-enzyme cascade. The multi-enzyme cascade includes a first enzyme attached to the first EutM subunit and a second enzyme attached to the second EutM subunit. The scaffold may be formed by a method that generally includes incubating a plurality of EutM subunits under conditions allowing the EutM subunits to self-assemble into a protein scaffold, attaching a first enzyme of a multi-enzyme cascade to a first EutM subunit, and attaching a second enzyme of the multi-enzyme cascade to a second EutM subunit. The scaffold may be self-assembled in vivo or in vitro. Each enzyme may be, independently of any other enzyme, attached to its EutM subunit in vivo or in vitro. Each enzyme may be, independently of any other enzyme, attached to its EutM subunit before or after the scaffold is assembled.

The invention is related to the fully effective gastro-protected universal oral delivery device of gastro-protected nanoparticles for the transport of intact biologically active polypeptides into the circulatory system. This universal oral delivery device is made of gastro-protected nanoparticles that transport intact therapeutic polypeptides through the gastrointestinal system and it successfully performs the paracellular transepithelial passage of all therapeutic polypeptides from the intestinal lumen into the circulatory system, fully preserving the integrity and biological activity of those therapeutic polypeptides.

The present invention provides, in various embodiments, genetically modified aerobic bacteria, polynucleotides and methods for expressing and/or harvesting electrically conductive protein nanowires (e-PNs). The present invention also provides e-PNs produced using the genetically modified aerobic bacteria, polynucleotides and methods.