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US 8,829,173 B2Granted
Recombinant vectors
AssigneeTocagen Inc.
InventorsHarry E. Gruber, Douglas J. Jolly, Omar D. Perez, Christopher R. Logg
Life of this patent
Estimating the term…
Abstract
This disclosure provides recombinant replication competent retroviral vectors having increased stability. The disclosure further relates compositions and uses of such vectors in the treatment of disease and disorders.
Claims33
A recombinant replication competent retrovirus comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a retroviral polynucleotide sequence comprising a Long-Terminal Repeat (LTR) sequence at the 3′ end of the retroviral polynucleotide sequence, wherein the 3′ LTR comprises a sequence that is at least 98% identical to the sequence from about nucleotide 9405 to about 9998 of SEQ ID NO:19 or 22, a promoter sequence at the 5′ end of the retroviral polynucleotide sequence, said promoter being suitable for expression in a mammalian cell, a gag nucleic acid domain, a pol nucleic acid domain and an env nucleic acid domain, wherein the promoter, gag, pol and env domains comprise a sequence that is at least 98% identical to the sequence from about 1 to about 8323 of SEQ ID NO:19 or 22 and wherein the retroviral polynucleotide sequence lacks 70 base pairs of MLV sequence downstream from the 3′LTR compared to a pACE vector of SEQ ID NO:21;
- a cassette comprising an internal ribosome entry site (IRES) comprising a sequence that is at least 98% identical to the sequence from about 8327 to 8876 of SEQ ID NO:19 or 22, operably linked to a heterologous polynucleotide, wherein the cassette is positioned 5′ to the 3′ LTR and 3′ to the env nucleic acid domain encoding the retroviral envelope and wherein SEQ ID NO:
- 19 and 22 lack small repeats on either side of the cassette compared to the pACE vector of SEQ ID NO:21;
- and
- cis-acting sequences necessary for reverse transcription, packaging and integration in a target cell,
- wherein the RCR maintains higher replication competency after 6 passages compared to a pACE vector comprising SEQ ID NO:21.
6 more elements
Dependencies are inferred from the claim text.