US 12,319,927 B2
Genetic construct
Michael McDonald, Guildford (GB)
Assigned to Healing Genes LLC, New York, NY (US); and Panacea Venture Healthcare Fund I, LP, Shanghai (CN)
Appl. No. 16/616,302
Filed by Healing Genes LLC, New York, NY (US); and Panacea Venture Healthcare Fund I, LP, Shanghai (CN)
PCT Filed May 25, 2018, PCT No. PCT/GB2018/051428
§ 371(c)(1), (2) Date Nov. 22, 2019,
PCT Pub. No. WO2018/215787, PCT Pub. Date Nov. 29, 2018.
Claims priority of application No. 1708385 (GB), filed on May 25, 2017.
Prior Publication US 2020/0157569 A1, May 21, 2020
Int. Cl. C12N 15/86 (2006.01); A61K 48/00 (2006.01); A61P 25/28 (2006.01); C12N 9/02 (2006.01); C12N 9/78 (2006.01)
CPC C12N 15/86 (2013.01) [A61P 25/28 (2018.01); C12N 9/0071 (2013.01); C12N 9/78 (2013.01); C12Y 114/16002 (2013.01); C12Y 305/04016 (2013.01); A61K 48/00 (2013.01); C12N 2750/14132 (2013.01); C12N 2750/14143 (2013.01)] 14 Claims
 
1. A genetic construct comprising;
a promoter operably linked to a first coding sequence, which encodes tyrosine hydroxylase (TH) and a second coding sequence, which encodes GTP cyclohydrolase 1 (GCH1);
wherein the first coding sequence comprises a sequence of SEQ ID NO: 1 or SEQ ID No: 2, or a fragment or variant thereof having greater than 85% sequence identity to SEQ ID No: 1 or SEQ ID No: 2; or a nucleotide sequence encoding an amino acid sequence as set out in SEQ ID NO: 21 or SEQ ID No: 22, or a fragment or variant thereof having greater than 85% sequence identity to SEQ ID No: 21 or SEQ ID No: 22; wherein the second coding sequence comprises a sequence of SEQ ID NO: 4, or a fragment or variant thereof having greater than 85% sequence identity to SEQ ID No: 4; or a nucleotide sequence encoding an amino acid sequence as set out in SEQ ID NO: 23, or a fragment or variant thereof having greater than 85% sequence identity to SEQ ID No: 23;
wherein the second coding sequence is 3′ to the first coding sequence and the first and second coding sequences are part of a single operon;
wherein the genetic construct further comprises between the first and second coding sequences a sequence encoding a 2A peptide spacer so as to encode a fusion protein in which the TH protein is fused to the GCH1 protein via the 2A peptide spacer that is cleavable to thereby yield a functional TH protein and a functional GCH1 protein; and
wherein the genetic construct does not encode aromatic amino acid decarboxylase (AADC).