Lipid membrane structure having intranuclear migrating property

Abstract

A lipid membrane structure for delivering a substance into a nucleus of a cell, wherein lipid membrane is modified with (a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and/or (b) a polypeptide consisting of an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 1, but including deletion and/or substitution and/or insertion of one or several amino acid residues, and having an activity of promoting migration of the lipid membrane structure into a nucleus of a cell, which can efficiently deliver a nucleic acid into a nucleus of an immunocyte such as dendritic cell.

1 . A lipid membrane structure for delivering a substance into a nucleus of a cell, the lipid membrane structure comprising a lipid membrane that
 encapsulates the substance to be delivered, and   is modified with a variant polypeptide of SEQ ID NO: 1 having amino acid residues which consist of the amino acid residues in the amino acid sequence of SEQ ID NO: 1 in which one to three amino acid residues have been deleted, substituted, and/or inserted.   
     
     
         2 . The lipid membrane structure according to  claim 1 , wherein the lipid membrane structure is a liposome. 
     
     
         3 . The lipid membrane structure according to  claim 1 , wherein the cell is an immunocyte. 
     
     
         4 . The lipid membrane structure according to  claim 3 , wherein the immunocyte is a dendritic cell. 
     
     
         5 . The lipid membrane structure according to  claim 1 , wherein the variant polypeptide of SEQ ID NO: 1 is modified with a hydrophobic group, and the hydrophobic group is inserted into the lipid membrane. 
     
     
         6 . The lipid membrane structure according to  claim 1 , which has a polypeptide containing a plurality of contiguous arginine residues on the surface. 
     
     
         7 . The lipid membrane structure according to  claim 1 , which has a polyalkylene glycol on the surface. 
     
     
         8 . The lipid membrane structure according to  claim 1 , wherein a nucleic acid and a cationic polymer are enclosed in the inside of the lipid membrane structure. 
     
     
         9 . The lipid membrane structure according to  claim 1 , wherein the substance to be delivered is a nucleic acid encoding an antigen polypeptide to be presented on the surface of an immunocyte. 
     
     
         10 . The lipid membrane structure according to  claim 9 , wherein the nucleic acid is DNA, and the DNA does not contain CpG. 
     
     
         11 . The lipid membrane structure according to  claim 1 , wherein the variant polypeptide of SEQ ID NO: 1 has amino acid residues which consist of the amino acid residues in the amino acid sequence of SEQ ID NO: 1 in which one to three amino acids have been deleted. 
     
     
         12 . The lipid membrane structure according to  claim 1 , wherein the variant polypeptide of SEQ ID NO: 1 has amino acid residues which consist of the amino acid residues in the amino acid sequence of SEQ ID NO: 1 in which one to three amino acids have been substituted. 
     
     
         13 . The lipid membrane structure according to  claim 1 , wherein the variant polypeptide of SEQ ID NO: 1 has amino acid residues which consist of the amino acid residues in the amino acid sequence of SEQ ID NO: 1 in which one to three amino acids have been inserted. 
     
     
         14 . A pharmaceutical composition comprising the lipid membrane structure according to  claim 1  as an active ingredient.