Structured DNA Conjugates

Technology #18588

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Top-down sequence design strategy for arbitrary polyhedral DNA origami objects. (A) (i) Specification of the target geometry based on an arbitrary closed surface representation is used as input to the algorithm that generates oligonucleotide sequences from (ii-iii)single-stranded scaffold routing and (iv) staple assignment. Atomic structure is generated (v) assuming canonical B-form DNA geometry and compared with (vi) 3D reconstruction from cryo-electron microscopic imaging. (B) Model structures predicted for Platonic (blue), Archimedean (vermillion), Johnson (bluish green), Catalan (orange), and other polyhedra (reddish purple) generated using the procedure (not shown to size). Miscellaneous polyhedra include (first column) heptagonal bipyramid; enneagonal trapezohedron; small stellated dodecahedron, a type of Kepler-Poinsot solid: rhombic hexecontahedron, a type of zonohedron; Goldberg polyhedron with symmetry of papillomaviridae: (second column) double helix; nested cube; nested octahedron; torus; and double torus. Single-stranded poly-T loops are omitted. Platonic, Archimedean, and Johnson solids each have 52—bp edge length. Catalan solids and the first column of other polyhedra have minimum 42-bp edge length, and the second column of other polyhedra have minimum 31 -bp edge length.
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Inventors
Professor Mark Bathe
Department of Biological Engineering, MIT
External Link (lcbb.mit.edu)
Sakul Ratanalert
Department of Chemical Engineering, MIT
Remi Veneziano
Department of Biological Engineering, MIT
Managed By
Tod Woolf
MIT Technology Licensing Officer
Patent Protection

Stable Nanoscale DNA Assemblies and Methods Thereof

Provisional Patent Application Filed

Applications

This invention is a method to produce varied DNA nanostructures useful in applications including drug delivery, immune stimulations for vaccines, sensing, or to mimic biological structures.

Problem Addressed

The field of DNA nanotechnology has been vastly expanded in recent years allowing target shapes to be programmed from the bottom-up using complementary Watson-Crick base pairing. For instance, scaffolded DNA origami is a powerful means of creating structured DNA assemblies, but it requires complex scaffold routing and staple design to realize a limited scope of target geometries. Furthermore, only one approach offers a solution to the inverse problem of sequence design based on specification of target geometry, but it is only semi-automated and relies on single duplex DNA arms and multi-junctions to represent polyhedral geometries, which may result in compliant and unstable assemblies that are unsuitable for many applications. This invention is a top-down design algorithm for programming arbitrary 3D geometries using DNA.

Technology

This method provides the nucleic acid sequences required to form a specific geometric form. A user inputs the geometric parameters of the desired structure and may also optionally define the physical size or template sequence of the object. This strategy can produce any geometric surface including non-spherical topologies such as a torus, provided that it can be rendered using polyhedral surface meshes. File formats containing specifications of the target object are converted into a set of arrays, providing input to a scaffold routing and staple design procedure. A polyhedral mesh is created and used to make a graph of the targeted structure to which equations are applied to determine scaffold routing. Ultimately, positions and orientations of each nucleotide are modeled to predict the 3D structure with full control over DNA sequence. This method produces high fidelity structures which are stable under low salt conditions, an important feature for in vitro applications.

Advantages

  • No reliance on user feedback; effiecient
  • Not limited to spherical topologies as with other methods; can produce any geometric surface
  • Control over physical size and DNA sequence
  • High fidelity structures; stable under low salt conditions