DNA Antibody Constructs And Method Of Using Same

Abstract

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.

1 . A nucleic acid molecule encoding a synthetic antibody comprising one or more nucleic acid sequences selected from the group consisting of:
 (a)   (b) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 67, a fragment of a nucleotide sequence that encodes SEQ ID NO: 67, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 67;   (c) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 69, a fragment of a nucleotide sequence that encodes SEQ ID NO: 69, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 69;   (d) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 71, a fragment of a nucleotide sequence that encodes SEQ ID NO: 71, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 71;   (e) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 73, a fragment of a nucleotide sequence that encodes SEQ ID NO: 73, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 73;   (f) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 75, a fragment of a nucleotide sequence that encodes SEQ ID NO: 75, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 75;   (g) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 77, a fragment of a nucleotide sequence that encodes SEQ ID NO: 77, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 77; and   (h)   (i)   (j) a nucleic acid sequence that is at least 80% homologous to a nucleotide sequence that encodes SEQ ID NO: 65, a fragment of a nucleotide sequence that encodes SEQ ID NO: 65, a nucleic acid sequence that is at least 80% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 65.   
     
     
         2 . (canceled) 
     
     
         3 . A nucleic acid molecule encoding a synthetic antibody comprising one or more nucleic acid sequences selected from the group consisting of:
 (a)   (b) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 68, a fragment of an amino acid sequence that encodes SEQ ID NO: 68, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 68;   (c) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 70, a fragment of an amino acid sequence that encodes SEQ ID NO: 70, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 70;   (d) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 72, a fragment of an amino acid sequence that encodes SEQ ID NO: 72, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 72;   (e) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 74, a fragment of an amino acid sequence that encodes SEQ ID NO: 74, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 74;   (f) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 76, a fragment of an amino acid sequence that encodes SEQ ID NO: 76, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 76;   (g) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 78, a fragment of an amino acid sequence that encodes SEQ ID NO: 78, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 78; and   (h)   (i)   (j) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 66, a fragment of an amino acid sequence that encodes SEQ ID NO: 66, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 66.   
     
     
         4 . (canceled) 
     
     
         5 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid sequence encodes a light chain polypeptide, a heavy chain polypeptide, both a light chain polypeptide and a heavy chain polypeptide, or fragments thereof. 
     
     
         6 . The nucleic acid molecule of  claim 5 , wherein when the nucleic acid sequence encodes a light chain polypeptide and a heavy chain polypeptide, the nucleic acid sequence also encodes a protease cleavage site. 
     
     
         7 . The nucleic acid molecule of  claim 6 , wherein the protease cleavage site is located between the light chain polypeptide and the heavy chain polypeptide and wherein the protease cleavage site includes a furin cleavage site and 2A peptide sequence. 
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule further encodes an immunoglobulin (Ig) signal peptide. 
     
     
         9 . The nucleic acid molecule of  claim 8 , wherein the Ig signal peptide comprises an IgE signal peptide. 
     
     
         10 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule comprises an expression vector. 
     
     
         11 . A composition comprising the nucleic acid molecule of  claim 1 . 
     
     
         12 . The composition of  claim 11  further comprising a pharmaceutically acceptable excipient. 
     
     
         13 . A method of preventing a disease in a subject in need thereof, the method comprising administering the nucleic acid molecule of  claim 1  to the subject. 
     
     
         14 . The method of  claim 13 , wherein the disease is infection by Chikagunya virus (CHIKV) or Dengue virus (DENV). 
     
     
         15 . The method of  claim 14 , wherein when the disease is infection by CHIKV, the nucleic acid sequence is selected from the group consisting of:
 (k)   (l)   (m) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 65, a fragment of a nucleotide sequence that encodes SEQ ID NO: 65, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 65.   
     
     
         16 . The method of  claim 14 , wherein when the disease is infection by DENV, the nucleic acid sequence is selected from the group consisting of:
 (n)   (o) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 67, a fragment of a nucleotide sequence that encodes SEQ ID NO: 67, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 67;   (p) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 69, a fragment of a nucleotide sequence that encodes SEQ ID NO: 69, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 69;   (q) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 71, a fragment of a nucleotide sequence that encodes SEQ ID NO: 71, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 71;   (r) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 73, a fragment of a nucleotide sequence that encodes SEQ ID NO: 73, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 73;   (s) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 75, a fragment of a nucleotide sequence that encodes SEQ ID NO: 75, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 75; and   (t) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 77, a fragment of a nucleotide sequence that encodes SEQ ID NO: 77, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 77.   
     
     
         17 . The method of  claim 14 , wherein when the disease is infection by CHIKV, the amino acid sequence is selected from the group consisting of:
 (u)   (v)   (w) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 66, a fragment of the amino acid sequence that encodes SEQ ID NO: 66, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 66.   
     
     
         18 . The method of  claim 14 , wherein when the disease is infection by DENV, the amino acid sequence is selected from the group consisting of:
 (x)   (y) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 68, a fragment of the amino acid sequence that encodes SEQ ID NO: 68, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 68;   (z) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 70, a fragment of the amino acid sequence that encodes SEQ ID NO: 70, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 70;   (aa) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 72, a fragment of the amino acid sequence that encodes SEQ ID NO: 72, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 72;   (bb) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 74, a fragment of the amino acid sequence that encodes SEQ ID NO: 74, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 74;   (cc) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 76, a fragment of the amino acid sequence that encodes SEQ ID NO: 76, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 76; and   (dd) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 78, a fragment of the amino acid sequence that encodes SEQ ID NO: 78, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 78.   
     
     
         19 . The method of  claim 13 , wherein administering includes at least one of electroporation and injection. 
     
     
         20 . A method of treating a disease in a subject in need thereof, the method comprising administering the nucleic acid molecule of  claim 1  to the subject. 
     
     
         21 . The method of  claim 20 , wherein the disease is infection by Chikagunya virus (CHIKV) or Dengue virus (DENV). 
     
     
         22 . The method of  claim 21 , wherein when the disease is infection by CHIKV, the nucleic acid sequence is selected from the group consisting of:
 (ee)   (ff)   (gg) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 65, a fragment of a nucleotide sequence that encodes SEQ ID NO: 65, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 65.   
     
     
         23 . The method of  claim 21 , wherein when the disease is infection by DENV, the nucleic acid sequence is selected from the group consisting of:
 (hh)   (ii) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 67, a fragment of a nucleotide sequence that encodes SEQ ID NO: 67, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 67;   (jj) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 69, a fragment of a nucleotide sequence that encodes SEQ ID NO: 69, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 69;   (kk) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 71, a fragment of a nucleotide sequence that encodes SEQ ID NO: 71, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 71;   (ll) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 73, a fragment of a nucleotide sequence that encodes SEQ ID NO: 73, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 73;   (mm) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 75, a fragment of a nucleotide sequence that encodes SEQ ID NO: 75, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 75; and   (nn) a nucleic acid sequence that is at least 80% homologous to the nucleotide sequence that encodes SEQ ID NO: 77, a fragment of a nucleotide sequence that encodes SEQ ID NO: 77, a nucleic acid sequence that is at least 80% homologous to a fragment of the nucleotide sequence that encodes SEQ ID NO: 77.   
     
     
         24 . The method of  claim 21 , wherein when the disease is infection by CHIKV, the amino acid sequence is selected from the group consisting of:
 (oo)   (pp)   (qq) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 66, a fragment of an amino acid sequence that encodes SEQ ID NO: 66, an amino acid sequence that is at least 80% homologous to a fragment of an amino acid sequence that encodes SEQ ID NO: 66.   
     
     
         25 . The method of  claim 21 , wherein when the disease is infection by DENV, the amino acid sequence is selected from the group consisting of:
 (rr)   (ss) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 68, a fragment of the amino acid sequence that encodes SEQ ID NO: 68, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 68;   (tt) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 70, a fragment of the amino acid sequence that encodes SEQ ID NO: 70, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 70;   (uu) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 72, a fragment of the amino acid sequence that encodes SEQ ID NO: 72, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 72;   (vv) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 74, a fragment of the amino acid sequence that encodes SEQ ID NO: 74, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 74;   (ww) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 76, a fragment of the amino acid sequence that encodes SEQ ID NO: 76, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 76; and   (xx) an amino acid sequence that is at least 80% homologous to SEQ ID NO: 78, a fragment of the amino acid sequence that encodes SEQ ID NO: 78, an amino acid sequence that is at least 80% homologous to a fragment of the amino acid sequence that encodes SEQ ID NO: 78.   
     
     
         26 . The method of  claim 20 , wherein administering includes at least one of electroporation and injection.