Methods for in vitro evolution of constructs derived from viruses
AssigneeMassachusetts Institute of Technology
InventorsDarrell J. Irvine, Ron Weiss, Yingzhong Li
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Abstract
The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.
Claims20
A nucleic acid molecule comprising a nucleotide sequence as shown in any one of SEQ ID NOs:
- 1-18, or any combination of two or more of SEQ ID NOs:
- 1-18.
A nucleic acid molecule comprising a portion of a nucleotide sequence as shown in any one of SEQ ID NOs:
- 1-18, or any combination of two or more portions of SEQ ID NOs:
- 1-18, wherein the portion of the nucleotide sequence comprises a combination of two or more mutations relative to the corresponding wild-type Venezuelan equine encephalitis (VEE) virus ribonucleic acid (RNA) selected from the group consisting of A1979G, G3936C, A4311G, A4758G, G4796T, and G4944A, wherein the position of the mutation(s) is relative to SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.