Human therapeutic targets and modulators thereof

Inventors

Biggins, John Baxter • BOWMAN, Brian Roger • Verdine, Gregory L.

Assignees

Lifemine Therapeutics Inc

Abstract

Among other things, the present disclosure provides technologies for efficient and effective identification of ETaGs, for example, from fungi genomes. In some embodiments, provided technologies are particularly useful for identifying mammalian targets of biosynthetic products of fungi. In some embodiments, provided technologies are particularly useful for identifying and/or prioritizing human targets for drug development. In some embodiments, provided technologies are particularly useful for developing modulators for human targets based on biosynthetic products of fungi.

Core Innovation

Embedded target genes (ETaGs) are described as non-biosynthetic genes that occur in or near fungal biosynthetic gene clusters and are optionally co-regulated with at least one biosynthetic gene in the cluster. An ETaG sequence is characterized by proximity to cluster genes and by being homologous to a mammalian nucleic acid sequence. The disclosure links ETaG↔human target homology to identifying and prioritizing human drug targets and developing modulators using fungal biosynthetic products or analogs.

The disclosure provides a database and system concept to search for ETaGs efficiently by restricting queries to biosynthetic cluster and proximity sequences and by indexing and annotating ETaGs. This search concept is described as enabling computational identification of embedded target gene sequences associated with fungal biosynthetic gene clusters and their human target homologs, while reducing false positives and improving computational efficiency.

The disclosure includes explicit example target families and associated pathways, including Sec7 and Ras, with Ras pathway domains such as RasGEF and RasGAP. Example fungal cluster-context ETaGs are discussed in connection with selecting and prioritizing homologous human targets, and the resulting cluster product or analog is described as being assayed for its effect on a human target.

Claims Coverage

The provided claim set includes four independent claims. Across them, the claims cover computational identification of ETaGs inside fungal biosynthetic gene cluster contexts and subsequent assaying of cluster products on human targets, modulation of a human target using a cluster product or analog where an ETaG in proximity is homologous to the human target, and database and system structures storing fungal biosynthetic gene cluster sequence sets on computer-readable media.

In the independent claims, the inventive subject matter centers on identifying ETaGs located in proximity to fungal biosynthetic gene clusters and homologous to mammalian human nucleic acid sequences, optionally using co-regulation with cluster genes; then linking the cluster product or analog to assaying its effect or modulating a human target, supported by database and system claims that store fungal biosynthetic gene cluster sequence sets on computer-readable media.

Stated Advantages

Documented Applications