Genetic construct
AssigneeQuethera Limited
InventorsPeter WIDDOWSON, Keith MARTIN
Life of this patent
Estimating the term…
Abstract
The invention provides genetic constructs and recombinant vectors comprising such constructs. The constructs and vectors can be used in gene therapy methods for treating a range of disorders, including glaucoma and deafness, or for promoting nerve regeneration and/or survival.
Claims49
A genetic construct comprising a promoter operably linked to a first coding sequence, which encodes the tyrosine kinase receptor B (TrkB), and a second coding sequence, which encodes an agonist of the TrkB receptor.
A genetic construct according to any preceding claim, wherein the genetic construct comprises a spacer sequence disposed between the first and second coding sequences, which spacer sequence encodes a peptide spacer that is configured to be digested to thereby produce the TrkB receptor and agonist as separate molecules.
A genetic construct according to any preceding claim, wherein the first coding sequence comprises a nucleotide sequence encoding the human canonical isoform of TrkB, optionally wherein the canonical isoform of TrkB comprises an amino acid sequence substantially as set out in SEQ ID NO. 9, or a fragment or variant thereof.
A genetic construct according to any preceding claim, wherein the first coding sequence comprises a nucleotide sequence which encodes isoform 4 of TrkB.
A genetic construct according to any preceding claim, wherein the first coding sequence comprises a nucleotide sequence encoding a mutant form of TrkB receptor, wherein one or more tyrosine residue at position 516, 701, 705, 706 and/or 816 of SEQ ID No:
- 9 is modified or mutated.
A genetic construct according to any preceding claim, wherein the second coding sequence encodes an agonist of the TrkB receptor, which is a member of the neurotrophin family of trophic factors, optionally wherein the agonist is selected from a group of agonists consisting of:
- Brain-derived neurotrophic factor (BDNF);
- nerve growth factor (NGF);
- neurotrophin-3 (NT-3);
- neurotrophin-4 (NT-4);
- and neurotrophin-5 (NT-5);
- or fragments thereof.
A genetic construct according to any preceding claim, wherein the agonist of the TrkB receptor is prepro-brain derived neurotrophic factor (pre-pro-BDNF), pro-BDNF or mature BDNF (mBDNF).
A genetic construct according to any preceding claim, wherein the second coding sequence comprises a nucleotide sequence encoding a signal peptide for the agonist of the TrkB receptor, most preferably a signal peptide for BDNF.
A genetic construct according to claim 36, wherein the second coding sequence comprises a nucleotide sequence substantially as set out in SEQ ID NO. 21, or a fragment or variant thereof.
A genetic construct according to any preceding claim, wherein the second coding sequence comprises a nucleotide sequence encoding a signal sequence peptide substantially as set out in any one of SEQ ID NO. 23, 25, 27 or 29, or wherein the signal peptide comprises an amino acid sequence substantially as set out in any one of SEQ ID NO. 22, 24, 26 or 28.
A genetic construct according to any preceding claim, wherein the second coding sequence comprises a nucleotide sequence encoding a signal sequence peptide substantially as set out in any one of SEQ ID NO. 31, 33, 35, 37, 39, 41, 43, 45, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101 or 103;
- or wherein the signal peptide comprises an amino acid sequence substantially as set out in any one of SEQ ID NO. 30, 32, 34, 36, 38, 40, 42, 44, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100 or 102.
A genetic construct according to any preceding claim, wherein the construct comprises a nucleotide sequence substantially as set out in SEQ ID No:
- 107 or 108, or a fragment or variant thereof.
Dependencies are inferred from the claim text.