Functionalized nanoparticles for intracellular delivery of biologically active molecules

Inventors

Aprikyan, Andranik Andrew • Dill, Kilian

Assignees

STEMGENICS Inc

Abstract

Functionalized biocompatible nanoparticles capable of penetrating through a mammalian cell membrane and delivering intracellularly a plurality of bioactive molecules for modulating a cellular function are disclosed herein The functionalized biocompatible nanoparticles comprise: a central nanoparticle ranging in size from about 5 to about 50 nm and having a polymer coating thereon, a plurality of functional groups covalently attached to the polymer coating, wherein the plurality of bioactive molecules are attached to the plurality of the functional groups, and wherein the plurality of bioactive molecules include at least a peptide and a protein, and wherein the peptide is capable of penetrating through the mammalian cell membrane and entering into the cell, and wherein the protein is capable of providing a new functionality within the cell. The protein may be a transcription factor selected from the group consisting of Oct4, Sox2, Nanog, Lin28, cMyc, and Klf4.

Core Innovation

The invention provides a functionalized biocompatible nanoparticle that penetrates through a mammalian cell membrane and delivers intracellularly a bioactive molecule for modulating a cellular function. The nanoparticle includes a central nanoparticle with one or more functional groups attached thereto, and a cell penetrating peptide attached to the central nanoparticle via a first linker molecule connected to a first functional group.

The same functionalized biocompatible nanoparticle also carries a bioactive molecule for modulating a function of the mammalian cell, attached via a second linker molecule to a second functional group on the central nanoparticle, independently from the attachment of the cell penetrating peptide. The central concept is linker-based covalent attachment of both a membrane-penetrating peptide and a protein cargo to the functionalized biocompatible nanoparticle.

The nanoparticle is described as supporting intracellularly active peptides and proteins, including transcription factors. Protein cargo examples include Oct4, Sox2, Nanog, Lin28, cMyc, and Klf4, and the invention describes nanoparticle-based intracellular delivery to modulate cellular functions and cell reprogramming without genome integration, with example embodiments including delivery of GFP.

Claims Coverage

The coverage centers on one independent claim that defines the structural arrangement of a central nanoparticle carrying both a cell penetrating peptide and a bioactive molecule via independently attached first and second linker molecules. The claim set includes dependent refinements that constrain size, coatings, materials, linker relationships, and specify transcription factors as the bioactive molecule.

Overall, the claim set provides structural coverage for a biocompatible nanoparticle with a functionalized central nanoparticle carrying both a cell-penetrating peptide and an intracellular bioactive cargo, each attached through independently defined first and second linker molecules, with dependent refinements specifying size, polymer coating, iron material, linker-length comparison, and transcription factor cargo.

Stated Advantages

Documented Applications