Nucleic Acids for Treatment of Allergies

Abstract

Nucleic acids (also referred to herein as “constructs”) that encode allergenic proteins, allergenic polypeptides, and allergenic peptides are provided. The nucleic acids are designed for delivery to immune cells and production of allergenic proteins, polypeptides, and peptides within those cells. The encoded proteins, polypeptides, and peptides have targeting sequences for targeting of the proteins to the MHC-II compartment for processing and display of one or more epitopes, resulting in an immune response to the epitope(s). In general, the nucleic acids comprise the following domains, which correlate to the respective domains of the encoded protein: a signal sequence domain; an intra-organelle stabilizing domain; an allergen domain; a transmembrane domain; and a cytoplasmic lysosome/endosome targeting domain.

1 - 14 . (canceled) 
     
     
         15 . A nucleic acid molecule comprising:
 a) a polynucleotide encoding signal sequence;   b) a polynucleotide encoding a lumenal domain of a lysosomal associated membrane (LAMP) protein;   c) a polynucleotide encoding an allergen domain of an allergen protein, wherein the nucleic acid sequence does not include a naturally-occurring signal sequence of the allergen protein and wherein said allergen protein comprises any of the following: Cry J1, Cry J2, Ara H1, Ara H2, Ara H3, Cry J3, CJP-4, CJP-6, CJP-8, CPA63, CJP38, Cha o 1, Jun a 1, Jun v 1, Cup a 1, Jun o 1, Cup s 1, Cha o 2, Jun a 2, Cup a 2, Jun a 3, Jun r 3, Cup s 3, Cup a 3, Ch4A, Ch4-1, PT-1, and/or LTP;   d) a polynucleotide encoding a transmembrane (TM) domain of a LAMP protein; and   e) a polynucleotide encoding a targeting domain (TG) domain of a LAMP protein,   wherein the LAMP protein is selected from LAMP-1, LAMP-2, CD63/LAMP-3, or DC-LAMP, LIMP II or Endolyn.   
     
     
         16 . The nucleic acid molecule of  claim 15 , wherein an expression vector comprises the nucleic acid molecule. 
     
     
         17 . The nucleic acid molecule of  claim 15 , wherein the nucleic acid molecule is DNA. 
     
     
         18 . A pharmaceutical composition comprising the nucleic acid molecule of  claim 15 . 
     
     
         19 . The pharmaceutical composition of  claim 18  further comprising a pharmaceutically acceptable carrier. 
     
     
         20 . A method of treating or preventing an allergic response to tree pollen in a subject in need thereof, the method comprising administering to the subject the nucleic acid molecule of  claim 15  in an amount effective to elicit an immune response.