THE GENOBOT PLATFORM

A programmable, non-viral delivery structure

Genobots are built by folding a gene-bearing DNA scaffold into a defined nanoscale structure using scaffolded DNA origami. Addressable positions on that structure are designed to hold the targeting and trafficking elements a program requires. The approach builds on more than a decade of foundational DNA-origami research at The Ohio State University.

WHY A NEW APPROACH

Established vectors carry structural constraints

Viral and lipid-based systems have enabled the first generation of approved genetic medicines. Their architecture, however, places limits on the diseases they can address.

Packaging capacity

Common viral vectors carry a limited genetic payload. Full-length dystrophin, for example, exceeds the payload capacity of AAV, which is why some approaches deliver shortened forms of a gene.

Immunogenicity

Pre-existing or treatment-induced immunity can restrict who is eligible for a viral therapy and whether it can be administered more than once.

Fixed tropism

Where a therapy is distributed is largely determined by the vector’s inherent properties rather than by design, which constrains both efficacy and exposure elsewhere.

Manufacturing route

Biological production systems introduce their own complexity. A synthetic route is being developed as an alternative approach to reproducible supply.

MECHANISM

How a Genobot is built and evaluated

Scaffolded DNA origami uses a long scaffold strand and short staple strands to fold DNA into a defined three-dimensional shape. The Genobot applies that principle so the therapeutic sequence is carried within a structure that can also hold functional elements at designed positions.

Electron micrograph of a folded DNA-origami hinge structure with a 50 nanometre scale bar

ELECTRON MICROGRAPH · DNA-ORIGAMI HINGE · SCALE BAR 50 NM

Transmission electron micrograph of folded DNA-origami structures

TRANSMISSION ELECTRON MICROGRAPH · FOLDED STRUCTURES

Rendered scaffolded DNA-origami nanotube structure

STRUCTURAL RENDER · NANOTUBE GEOMETRY

STAGE 01

Encode

A gene-bearing single-stranded DNA scaffold carries the therapeutic sequence.

STAGE 02

Fold

Staple strands direct self-assembly into a defined, reproducible nanoscale geometry.

STAGE 03

Functionalize

Targeting and trafficking elements are positioned at designed attachment sites.

STAGE 04

Deliver and evaluate

Uptake, delivery and expression are assessed in preclinical models. All work described on this page is preclinical.

DESIGN OBJECTIVES

Four objectives under preclinical evaluation

Each objective below describes design intent under preclinical evaluation, not an established capability.

01

Large-payload architecture

Designed to accommodate genetic constructs beyond the practical capacity of common viral vectors.

02

Programmable targeting

Defined attachment sites are intended to support controlled placement of targeting and functional elements.

03

Repeat-administration potential

A non-viral architecture being evaluated for tolerability and repeat administration.

04

Reproducible self-assembly

A design and manufacturing approach intended to support consistent assembly of structurally defined constructs.

IN CONTEXT

How the Genobot differs in design

The comparison below describes design intent, not head-to-head results. The Genobot is preclinical. AAV and lipid nanoparticle systems are clinically validated modalities with established strengths.

Genobot

DESIGN INTENT · PRECLINICAL

Structurally engineered, non-viral. Large-payload architecture and programmable attachment sites are design objectives under evaluation. Synthetic assembly route.

AAV

APPROVED MODALITY

Viral. Clinically validated for a range of indications. Limited packaging capacity and immune considerations can affect eligibility and re-administration.

LNP / mRNA