Targeted delivery of proteins across the blood-brain barrier
Embodiments of the invention are directed to compositions comprising a peptide sequence, or a nucleic acid encoding the same, wherein the peptide sequence includes a receptor-binding region of apolipoprotein E (apoE), or a sequence variant or fragment thereof, for directing delivery of a given protein or therapeutic across the blood brain barrier. Embodiments of the invention are also directed to methods of using the compositions for treating or preventing a neurological disorder, disease, or symptom in a subject in need thereof.
1. A composition comprising a peptide sequence, the peptide sequence comprising (1) an oligomer of a receptor-binding region of apolipoprotein E (apoE) and (2) a protein, wherein
the oligomer of the receptor-binding region of apoE is
(b) SEQ ID No: 19;
the peptide sequence does not comprise SEQ ID NO:14;
the peptide sequence does not comprise SEQ ID NO:15;
the composition is suitable for crossing the blood brain barrier; and
the peptide sequence is expressed as a fusion protein.
2. A composition comprising a nucleic acid molecule, wherein the nucleic acid molecule comprises a sequence encoding a peptide sequence of claim 1 .
3. A method of producing a genetically engineered cell line expressing the peptide sequence of claim 1 , the method comprising:
identifying a cell line of interest to be transformed;
introducing a nucleic acid molecule into the genetic material of a cell from the cell line of interest, wherein the nucleic acid molecule encodes a fusion protein comprising the peptide sequence of claim 1 ;
selecting for a successfully transformed cell; and
cloning the transformed cell, wherein the genetically engineered cell expresses the protein of interest.
4. The composition of claim 1 , wherein the peptide sequence is conjugated to an agent that mediates delivery to a target site.
5. The composition of claim 4 , wherein the agent that mediates delivery to a target site comprises nanoparticles or liposomes.
6. A composition comprising a peptide sequence, the peptide sequence comprising (1) an oligomer of a receptor-binding region of apolipoprotein E (apoE) and (2) a protein, wherein
the oligomer of the receptor-binding region of apoE is
(b) SEQ ID No: 19;
the peptide sequence does not comprise SEQ ID NO:14;
the peptide sequence does not comprise SEQ ID NO:15;
the composition is suitable for crossing the blood brain barrier;
the composition is (1) suitable for treating a neurological disorder, disease, or symptom thereof, (2) suitable for treating a lysosomal storage disease, or (3) both; and
the peptide sequence is expressed as a fusion protein.
7. The composition of claim 6 , wherein the peptide sequence is conjugated to an agent that mediates delivery to a target site.