Conjugate systems and methods of use thereof

Inventors

CURIEL, David • Lu, Zhi Hong

Assignees

Washington University in St. Louis

Abstract

Among the various aspects of the present disclosure is the provision of conjugate systems and methods of use thereof. In an aspect, the conjugate system includes an adenovirus comprising an exterior surface, and at least one polypeptide comprising a first domain and a second domain, and wherein the exterior surface comprises a peptide tag capable of binding to a binding partner.

Core Innovation

The disclosure describes conjugate systems that use an adenovirus with an exterior surface comprising a hexon protein surface and a fiber knob surface. The exterior surface comprises a peptide tag capable of binding to a binding partner, and the systems further include at least one polypeptide having a first domain and a second domain, where the first domain comprises the binding partner and the second domain comprises a Cas protein.

In one implementation, the adenovirus is engineered to display peptide tags on the hexon protein surface and/or the fiber knob surface and to couple a Cas protein configured as a binding-partner fusion. This design is described in the context of providing intracellular delivery using an empty capsid and coupling via binding between a peptide tag and its corresponding binding partner, including examples of SpyTag/SpyCatcher, DogTag/DogCatcher, and SnoopTag/SnoopCatcher.

In another implementation, an adenovirus conjugate system displays a peptide tag on an exterior surface that includes a hexon protein surface and a protein IX surface. The at least one polypeptide includes a first domain comprising a binding partner and a second domain comprising an mRNA-binding domain, enabling coupling of the adenovirus to mRNA.

Claims Coverage

The partial claim set includes two independent claims centered on adenovirus-displayed peptide tags that bind a binding partner provided by a first polypeptide domain. One independent claim is directed to a polypeptide whose second domain comprises a Cas protein, and another is directed to a polypeptide whose second domain comprises an mRNA-binding domain.

Across the independent claims, the shared inventive structure is an adenovirus exterior surface presenting a peptide tag that binds to a corresponding binding partner on a polypeptide. The divergence is the second domain on the polypeptide: Cas protein in one claim and an mRNA-binding domain in the other.

Stated Advantages

Documented Applications