Methods of transduction using a viral vector and inhibitors of antiviral restriction factors
AssigneeSana Biotechnology, Inc.
InventorsMariliis OTT, Daryl HUMES, Neal VAN HOEVEN
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Abstract
Provided herein are methods of transducing or delivering an exogenous agent to a cell using a viral vector pseudotyped with a paramyxovirus and an inhibitor of the mammalian target of rapamycin (mTOR). In some embodiments, the methods can further include the administration of an antiviral restriction factor inhibitor and/or a cytokine.
Claims176
A method of transducing cells in subject, the method comprising:
- (a) administering to a subject an inhibitor of the mammalian target of rapamycin (mTOR), and
- (b) administering to the subject a viral vector comprising a viral fusogen embedded in the lipid bilayer.
A method of delivering an exogenous agent to a subject, the method comprising:
- (a) administering to a subject an inhibitor of mTOR, and
- (b) administering to the subject a viral vector comprising an exogenous agent, wherein the viral vector comprises a fusogen embedded in the lipid bilayer.
A method of transducing cells in a subject, the method comprising
- (a) administering to a subject an inhibitor of the mammalian target of rapamycin (mTOR), and
- (b) administering to the subject a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof wherein the vector comprises a polynucleotide encoding a chimeric antigen receptor (CAR), and
- (c) administering to the subject IL-7 or a functional variant thereof.
A method of transducing cells in a subject, the method comprising
- (a) administering to a subject an inhibitor of the mammalian target of rapamycin (mTOR), and
- (b) administering to the subject a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof wherein the vector comprises
- (i) a viral VPX protein, and
- (ii) a polynucleotide encoding a chimeric antigen receptor (CAR).
A method of transducing cells in subject, the method comprising:
- (a) administering to a subject an inhibitor of an antiviral restriction factor, and
- (b) administering to the subject a viral vector comprising a viral fusogen embedded in the lipid bilayer.
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a viral vector and an inhibitor of mTOR to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject.
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a viral vector and an inhibitor of mTOR that is temsirolimus to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject.
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a viral vector and an inhibitor of an antiviral restriction factor to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject.
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a viral vector and a polyene antifungal agent to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject.
A method for administering a viral vector to a subject, the method comprising:
- (a) obtaining whole blood from a subject;
- (b) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (c) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector and an inhibitor of mTOR to create a transduction mixture;
- and
- (d) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(d) are performed in-line in a closed fluid circuit.
A method for administering a viral vector to a subject, the method comprising:
- (a) obtaining whole blood from a subject;
- (b) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (c) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector and an inhibitor of an antiviral restriction factor to create a transduction mixture;
- and
- (d) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(d) are performed in-line in a closed fluid circuit.
A method for administering a viral vector to a subject, the method comprising:
- (a) administering to a subject an inhibitor of mTOR;
- (b) obtaining whole blood from a subject;
- (c) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (d) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector to create a transduction mixture;
- and
- (e) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(e) are performed in-line in a closed fluid circuit.
A method for administering a viral vector to a subject, the method comprising:
- (a) administering to a subject an inhibitor of an antiviral restriction factor;
- (b) obtaining whole blood from a subject;
- (c) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (d) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector to create a transduction mixture;
- and
- (e) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(e) are performed in-line in a closed fluid circuit.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) contacting PBMCs or a subset thereof from a subject with a viral vector and an inhibitor of mTOR to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (b) administering the transduction mixture to the subject, thereby administering the exogenous agent to the subject.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) contacting PBMCs or a subset thereof from a subject with a viral vector and an inhibitor of mTOR that is temsirolimus to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (b) administering the transduction mixture to the subject, thereby administering the exogenous agent to the subject.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) contacting PBMCs or a subset thereof from a subject with a viral vector and an inhibitor of an antiviral restriction factor to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (b) administering the transduction mixture to the subject, thereby administering the exogenous agent to the subject.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) contacting PBMCs or a subset thereof from a subject with a viral vector and a polyene antifungal agent to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (b) administering the transduction mixture to the subject, thereby administering the exogenous agent to the subject.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) obtaining whole blood from a subject;
- (b) collecting from the whole blood a fraction of blood containing peripheral blood mononuclear cells (PBMCs) or a subset thereof;
- (c) contacting the fraction of blood containing peripheral blood mononuclear cells (PBMCs) or a subset thereof with a viral vector and an inhibitor of mTOR to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (d) reinfusing the transduction mixture to the subject, thereby administering the exogenous agent to the subject,
- wherein steps (a)-(d) are performed in-line in a closed fluid circuit.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) obtaining whole blood from a subject;
- (b) collecting from the whole blood a fraction of blood containing peripheral blood mononuclear cells (PBMCs) or a subset thereof;
- (c) contacting the fraction of blood containing peripheral blood mononuclear cells (PBMCs) or a subset thereof with a viral vector and an inhibitor of an antiviral restriction factor to create a transduction mixture, wherein the viral vector comprises an exogenous agent;
- and
- (d) reinfusing the transduction mixture to the subject, thereby administering the exogenous agent to the subject,
- wherein steps (a)-(d) are performed in-line in a closed fluid circuit.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) administering to the subject inhibitor of mTOR;
- (b) obtaining whole blood from a subject;
- (c) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (d) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector to create a transduction mixture;
- and
- (e) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(e) are performed in-line in a closed fluid circuit.
A method for delivering an exogenous agent to a subject, the method comprising:
- (a) administering to the subject inhibitor of an antiviral restriction factor;
- (b) obtaining whole blood from a subject;
- (c) collecting from the whole blood a fraction of blood containing PBMCs or a subset thereof;
- (d) contacting the fraction of blood containing PBMCs or a subset thereof with a viral vector to create a transduction mixture;
- and
- (e) reinfusing the transduction mixture to the subject, thereby administering the viral vector to the subject,
- wherein steps (a)-(e) are performed in-line in a closed fluid circuit.
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, an inhibitor of an antiviral restriction factor, and Il-7 or a functional variant thereof to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a chimeric antigen receptor (CAR).
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof and an inhibitor of an antiviral restriction factor, to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a viral VPX protein and a chimeric antigen receptor (CAR).
A method for transducing cells in a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, and an inhibitor of an antiviral restriction factor to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a viral VPX protein and a chimeric antigen receptor (CAR).
A method for transducing cells in a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, an inhibitor of an antiviral restriction factor, and Il-7 or a functional variant thereof to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a chimeric antigen receptor (CAR).
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, an inhibitor of mTOR, and Il-7 or a functional variant thereof to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a chimeric antigen receptor (CAR).
A method for administering a viral vector to a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof and an inhibitor of mTOR, to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a viral VPX protein and a chimeric antigen receptor (CAR).
A method for transducing cells in a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, and an inhibitor of mTOR to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a viral VPX protein and a chimeric antigen receptor (CAR).
A method for transducing cells in a subject, the method comprising:
- (a) contacting peripheral blood mononuclear cells (PBMCs) or a subset thereof from a subject with a composition comprising a lentiviral vector comprising one or more Nipah envelope proteins or functional variants thereof, an inhibitor of mTOR, and Il-7 or a functional variant thereof to create a transduction mixture;
- and
- (b) administering the transduction mixture to the subject, thereby administering the viral vector to the subject, wherein the vector comprises a chimeric antigen receptor (CAR).
The method of 1-3, 6-61, 66-127, wherein the viral fusogen is a baboon endogenous virus (BaEV) envelope glycoprotein.
The method of 1-3, 6-61, 66-127, wherein the viral fusogen is a Cocal virus envelope glycoprotein.
The method of 1-3, 6-61, 66-127, wherein the viral fusogen is an Alphavirus class II fusion protein or a functional variant thereof, optionally wherein the Alphavirus is a Sindbis virus.
The method of 1-3, 6-61, 66-127, wherein the viral fusogen comprises a Paramyxovirus fusion (F) protein or a biologically active portion thereof, optionally wherein the Paramyxovirus is a Morbillivirus or a Henipavirus.
A composition comprising a leukapheresis composition for delivering a viral vector to a subject, wherein the leukapheresis composition comprises peripheral blood mononuclear cells (PBMCs) or a subset thereof from the subject, a viral vector, and an inhibitor of mTOR.
A composition comprising a leukapheresis composition for delivering a viral vector to a subject, wherein the leukapheresis composition comprises peripheral blood mononuclear cells (PBMCs) or a subset thereof from the subject, a viral vector, and an inhibitor of an antiviral restriction factor.
Dependencies are inferred from the claim text.