Methods and compositions for improved retroviral gene and drug delivery
OwnerLorraine Albrittoninventor
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Abstract
The present invention provides recombinant viral particles for gene therapy and liposome compositions for drug delivery comprising an env protein of MMTV. The invention also provides retroviral or lentiviral env proteins comprising a mutation in a receptor-binding motif. The invention also provides nucleic acids, proteins, and compositions comprising the recombinant viral particles, nucleic acids, and proteins. The invention also provides methods for enhancing delivery of a gene or compound of interest to a target cell, and methods for targeting a compound of interest to an acidified compartment of a cell.
Claims34
An isolated nucleic acid encoding for a receptor-binding motif of an MMTV env protein, said isolated nucleic acid having a nucleotide sequence selected from the sequences set forth in SEQ ID No 3-8, 17, 18, and 26.
An isolated nucleic acid encoding an MMTV env protein, said isolated nucleic acid comprising a mutation in a receptor-binding motif (RBM) of said env protein, said RBM having a nucleic acid sequence selected from the sequences set forth in SEQ ID No 3-8, 17, 18, and 26.
A method for delivering a nucleic acid of interest or compound of interest to a target cell, comprising contacting said target cell with a recombinant viral particle or liposome comprising:
- a. a nucleic acid of interest or compound of interest;
- and
- b. a mutated retroviral or lentiviral env protein comprising a heterologous peptide;
- whereby said heterologous peptide mediates uptake of said recombinant viral particle or liposome via a cellular target molecule, thereby delivering a nucleic acid of interest to a target cell.
A method for enhancing an ability of a recombinant retroviral or lentiviral particle to infect a target cell, comprising contacting said target cell with an inhibitor of a lysosomal protease, whereby said inhibitor of a vacuolar enzyme prevents or impedes intracellular degradation of said recombinant retroviral or lentiviral particle, thereby enhancing delivery of a recombinant retroviral or lentiviral particle to a target cell.
An isolated nucleic acid encoding for a heparin-binding motif of an MMTV env protein, said isolated nucleic acid having a nucleotide sequence selected from the sequences set forth in SEQ ID No 27-32, 56-61, and 82.
An isolated nucleic acid encoding for a receptor-binding motif of an MoMLV env protein, said isolated nucleic acid having a nucleotide sequence selected from the sequences set forth in SEQ ID No 70-75.
An isolated nucleic acid encoding a mutated MoMLV env protein, said isolated nucleic acid comprising a mutation in a receptor-binding motif (RBM) of said env protein, said RBM having a nucleic acid sequence selected from the sequences set forth in SEQ ID No 70-75.
A method for delivering a nucleic acid of interest or compound of interest to a tar-et cell via a clathrin-independent endocytosis, comprising contacting said target cell with a recombinant viral particle comprising:
- a. a nucleic acid of interest or compound of interest;
- and
- b. a mutated version of a wild-type env protein, wherein viruses containing said wild-type env protein are internalized via a clathrin-dependent endocytosis, and wherein said mutated version of a wild-type env protein comprises an insertion of a heterologous peptide that binds a cellular surface protein that capable of being internalized via a clathrin-independent endocytosis,
- thereby delivering a nucleic acid of interest or compound of interest to a target cell via a clathrin-independent endocytosis.
A method for delivering a nucleic acid of interest or compound of interest to a target cell via a clathrin-dependent endocytosis, comprising contacting said target cell with a recombinant viral particle comprising:
- a. a nucleic acid of interest or compound of interest;
- and
- b. a mutated version of a wild-tape env protein, wherein viruses containing said wild-type env protein are internalized via a clathrin-independent endocytosis, and wherein said mutated version of a wild-type env protein comprises an insertion of a heterologous peptide that binds a cellular surface protein that capable of being internalized via a clathrin-dependent endocytosis,
- thereby delivering a nucleic acid of interest or compound of interest to a target cell via a clathrin-dependent endocytosis.
Dependencies are inferred from the claim text.