Molecular sleds and uses thereof
The present invention relates to compositions which may comprise a molecular sled linked to cargo and uses thereof. In particular, the present invention relates to a non-naturally occurring or engineered composition which may comprise a molecular sled, linkers and a molecular cargo connected to the sled via the linkers. Methods involving the use of molecular sleds and their cargoes and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.
1. A non-naturally occurring or engineered composition comprising:
(a) a molecular sled comprising a core sequence of amino acids, wherein the core sequence is KKRRRCX″ (SEQ ID NO: 2), or KKRRRCF (SEQ ID NO: 4), wherein X″ is any amino acid;
(b) one or more linkers comprising one or more amino acids; and
(c) a molecular cargo linked to the one or more linkers; and
wherein the core sequence of amino acids KKRRRCX″ (SEQ ID NO: 2), or KKRRRCF (SEQ ID NO: 4) is capable of sliding on a negatively charged polymer track.
2. The composition of claim 1 , further comprising a nuclear localization signal (NLS).
3. The composition of claim 1 , wherein the one or more linkers are attached with a covalent bond, a non-covalent bond, or a neutrally charged ionic bond.
4. The composition of claim 1 , further comprising a molecular capsule, a small molecule, a nucleic acid, a peptide, a protein or an analog or derivative thereof.
5. The composition of claim 1 , wherein the molecular cargo is chemically modified with one or more gyrase inhibitors.
6. The composition of claim 1 , further comprising a molecular capsule, cyclodextrin or pillararene.
7. The composition of claim 1 , wherein the molecular cargo is covalently linked to the one or more linkers.
8. The composition of claim 1 , wherein the negatively charged track is double stranded DNA, single stranded DNA, engineered DNA nanostructures, a nucleosome, chromatin, or other natural or engineered DNA-protein complex, RNA, a ribosome or other natural or engineered ribonucleoprotein complex, a synthetic polymer or a natural polymer, organic nanowires or surfaces, inorganic nanowires or surfaces.
9. The composition of claim 1 , further comprising one or more additional sleds, linkers or cargo.
10. The composition of claim 1 , further comprising a peptide nucleic acid (PNA) brake or a sled-PNA conjugate.
11. The composition of claim 4 , wherein the small molecule is a drug.
12. The composition of claim 6 , wherein the molecular capsule is calixarene or cucurbituril.
13. The composition of claim 8 , wherein the engineered DNA nanostructure is DNA origami, the synthetic polymer is polyglutamic acid or the natural polymer is actin or tubulin.
14. The composition of claim 10 , wherein the sled-PNA conjugate is a chromatin modifying factor.