Compositions and methods for cell delivery
The present disclosure described herein provides compositions with a membrane-penetrating properties and methods for allowing translocation across a membrane without disruption.
1. A pharmaceutical composition comprising:
a polypeptide comprising at least one sequence of AB n C, wherein A is selected from a hydrophobic amino acid or an amide containing backbone with a nucleic acid side chain; B and C may be the same or different, and are independently selected from arginine, asparagine, glutamine, lysine, and analogs thereof; X is an amide containing backbone with a nucleic acid side chain; and n is an integer from 1 to 4; and at least one heterologous moiety.
2. The composition of claim 1 , wherein the heterologous moiety is selected from the group consisting of a small molecule, a peptide, a peptide nucleic acid (PNA), and a nucleic acid.
3. The composition of claim 1 , wherein the heterologous moiety possesses at least one effector activity selected from the group consisting of modulates a biological activity, binds a regulatory protein, modulates enzymatic activity, modulates substrate binding, modulates receptor activation, modulates protein stability/degradation, and modulates transcript stability/degradation.
4. The composition of claim 1 , wherein the heterologous moiety is cleavable.
5. The composition of claim 3 , wherein the heterologous moiety is selected from the group consisting of an epigenetic modifying agent, epigenetic enzyme, a bicyclic peptide, a transcription factor, a DNA or protein modification enzyme, a DNA-intercalating agent, an efflux pump inhibitor, a nuclear receptor activator or inhibitor, a proteasome inhibitor, a competitive inhibitor for an enzyme, a protein synthesis inhibitor, a nuclease, a protein fragment or domain, a tag or marker, an antigen, an antibody or antibody fragment, a ligand or a receptor, a synthetic or analog peptide from a naturally-bioactive peptide, an anti-microbial peptide, a pore-forming peptide, a targeting or cytotoxic peptide, a degradation or self-destruction peptide, a CRISPR component system or component thereof, DNA, RNA, artificial nucleic acids, a nanoparticle, an oligonucleotide aptamer, a peptide aptamer, and an agent with poor pharmacokinetics or pharmacodynamics (PK/PD).
6. The composition of claim 1 , wherein B is selected from arginine or glutamine.
7. The composition of claim 1 , wherein C is arginine.
8. The composition of claim 1 , wherein n is 2.
9. The composition of claim 1 , wherein the polypeptide has a size in the range of about 5 to about 50 amino acid units in length.
10. The composition of claim 1 comprising two or more polypeptides that are linked to one another.
11. The composition of claim 1 , wherein A is phenylalanine.
12. The composition of claim 1 , wherein B is glutamine.
13. The composition of claim 1 , wherein X is uracil.
14. The composition of claim 1 , wherein n is 1.
15. The composition of claim 1 , wherein A is phenylalanine, B is glutamine, X is uracil, C is arginine, and n is 1.
16. The composition of claim 1 , wherein A is phenylalanine and X is uracil.