Chimeric alphavirus replicon particles
AssigneeNovartis Vaccines and Diagnostics, Inc.
InventorsJohn M. Polo, Silvia Perri, Kent Thudium
Life of this patent
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Abstract
Chimeric alphaviruses and alphavirus replicon particles are provided including methods of making and using same. Specifically, alphavirus particles are provided having nucleic acid molecules derived from one or more alphaviruses and structural proteins (capsid and/or envelope) from at least two or more alphaviruses. Methods of making, using, and therapeutic preparations containing the chimeric alphavirus particle, are disclosed.
Claims55
A chimeric alphavirus particle, comprising:
- RNA derived from one or more alphaviruses;
- and
- a capsid protein, wherein said capsid protein is derived from two or more different alphaviruses.
A chimeric alphavirus particle comprising RNA derived from a first alphavirus and structural proteins, wherein said structural proteins comprise:
- (a) a hybrid capsid protein having (i) an RNA binding domain derived from said first alphavirus and (ii) an envelope glycoprotein interaction domain derived from a second alphavirus which is different from the first alphavirus;
- and
- (b) an envelope glycoprotein derived from said second alphavirus.
A chimeric alphavirus particle comprising
- (1) RNA encoding one or more nonstructural proteins derived from a first alphavirus,
- (2) a packaging signal derived from a second alphavirus different from said first alphavirus, wherein said packaging signal is inserted into a site selected from the group consisting of the junction of nsP3 with nsP4 and a deletion in a nonstructural protein gene;
- (3) a capsid protein derived from said second alphavirus;
- and
- (4) an envelope protein derived from an alphavirus different from said first alphavirus.
A method for producing alphavirus replicon particles, comprising introducing into a host cell:
- a) an alphavirus replicon RNA derived from one or more alphaviruses, wherein said replicon RNA further comprises one or more heterologous sequence(s);
- and
- b) at least one separate defective helper RNA(s) encoding structural protein(s) absent from the replicon RNA, wherein one of said structural proteins is a capsid protein derived from two or more different alphaviruses,
- wherein alphavirus replicon particles are produced.
A method for producing alphavirus replicon particles, comprising introducing into a host cell:
- a) an alphavirus replicon RNA encoding one or more nonstructural proteins from a first alphavirus, a packaging signal derived from a second alphavirus which is different from the first alphavirus, and one or more heterologous sequence(s), wherein said packaging signal is inserted into a site selected from the group consisting of the junction of nsP3 with nsP4 and a deletion in a nonstructural protein gene;
- and
- b) at least one separate defective helper RNA(s) encoding structural protein(s) absent from the replicon RNA, wherein at least one of said structural proteins is a capsid protein derived from said second alphavirus, and at least one of said structural proteins is an envelope protein derived from an alphavirus different from said first alphavirus, wherein alphavirus replicon particles are produced.
Dependencies are inferred from the claim text.