Chimeric post-transcriptional regulatory element
The present disclosure relates to chimeric post-transcriptional regulatory elements (PRE) and vectors useful for expressing a protein in a cell. The PRE contains alpha, beta and optionally gamma subelements selected from different native PRE sequences and are discovered to be more potent than their native counterparts.
1. A polynucleotide comprising:
(a) a first fragment consisting of the nucleic acid sequence of SEQ ID NO: 7 or a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 7,
(b) a second fragment consisting of the nucleic acid sequence of SEQ ID NO: 9 or a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 9, and
(c) a third fragment consisting of the nucleic acid sequence of SEQ ID NO: 3 or a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 3.
2. The polynucleotide of claim 1 , wherein the second fragment is between the first fragment and the third fragment and each fragment is not more than 20 nucleotides away from a neighboring fragment.
3. A polynucleotide construct, comprising the polynucleotide of claim 1 and a protein-coding sequence.
4. The polynucleotide construct of claim 3 , further comprising a 3′-UTR.
5. The polynucleotide construct of claim 3 , further comprising a poly(A) sequence.
6. A cell, in culture, comprising the polynucleotide construct of claim 3 .