Compositions and methods for the prevention and treatment of rabies virus infection
Inventors
Wang, Nathaniel Stephen • Miyake-Stoner, Shigeki Joseph • Aliahmad, Parinaz • Geall, Andrew
Assignees
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Publication Number
US-11730804-B1
Publication Date
2023-08-22
Expiration Date
Abstract
The present disclosure relates generally to the field of molecular virology, and particularly relates to nucleic acid molecules encoding a modified alphavirus virus viral genome or self-replicating RNA (srRNA) construct, recombinant cells and pharmaceutical compositions containing the same, as well as the use of such nucleic acid molecules, recombinant cells and compositions for production of desired products in cell cultures or in a living body. Also provided are methods for eliciting an immune response in a subject in need thereof, as well as methods for preventing and/or treating rabies virus infection.
Core Innovation
The invention relates to rabies prevention and/or treatment using nucleic acid constructs comprising a modified alphavirus genome or self-replicating RNA (srRNA). The modified alphavirus genome or srRNA comprises no nucleic acid sequence encoding viral structural proteins required for viral particle formation, so viral structural proteins for viral particle formation are removed from the construct.
In the construct, the nucleic acid sequence encoding the viral structural proteins of the modified alphavirus genome or srRNA is replaced by a coding sequence for a polypeptide construct comprising an envelope glycoprotein G of rabies virus (RABV-G), a variant thereof, or an antigenic determinant of either thereof. The described approach includes defining and locating antigenic determinants within RABV-G, including specific antigenic sites, while maintaining the self-replicating function of the modified alphavirus genome.
The nucleic acid construct comprises the nucleic acid sequence of SEQ ID NO: 2 and SEQ ID NO: 3. The disclosure further includes embodiments relating to antigenic determinant localization on RABV-G, such as N-terminal half versus C-terminal half, and sequence-identity constraints tied to SEQ ID NOS: 6-11, along with recombinant cells and pharmaceutical compositions formulated with delivery vehicles.
Claims Coverage
The partial content identifies one independent claim. It covers an engineered nucleic acid construct using a modified alphavirus genome or srRNA backbone lacking viral structural protein sequences, with replacement by RABV-G or a variant or antigenic determinant, and inclusion of SEQ ID NO: 2 and SEQ ID NO: 3.
Modified alphavirus genome or srRNA lacking viral structural protein sequences for viral particle formation
A nucleic acid construct comprising a nucleic acid sequence encoding a modified alphavirus genome or self-replicating RNA (srRNA), wherein the modified alphavirus genome or srRNA comprises no nucleic acid sequence encoding viral structural proteins required for viral particle formation.
RABV-G replacement of viral structural protein coding sequence
The nucleic acid construct wherein the nucleic acid sequence encoding the viral structural proteins of the modified alphavirus genome or srRNA is replaced by a coding sequence for a polypeptide construct comprising an envelope glycoprotein G of a rabies virus (RABV-G), a variant thereof, or an antigenic determinant of either thereof.
Inclusion of SEQ ID NO: 2 and SEQ ID NO: 3
The nucleic acid construct wherein the nucleic acid construct comprises the nucleic acid sequence of SEQ ID NO: 2 and SEQ ID NO: 3.
Overall, the independent claim requires a modified alphavirus genome or srRNA with removal of structural protein sequences required for viral particle formation, replacement with an RABV-G, variant, or antigenic determinant coding sequence, and inclusion of SEQ ID NO: 2 and SEQ ID NO: 3.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Rabies prevention and/or treatment using nucleic acid constructs comprising modified alphavirus genomes or self-replicating RNA.
Inducing neutralizing antibody responses, as characterized by neutralizing antibody titer, including RFFIT in the described assessment.
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