Alphavax, Incorporated

Janssen Pharmaceuticals, Inc.

Harrisvaccines, Inc.

Synthetic Genomics, Inc.

Aphavax, Inc.

Kurt Iver Kamrud

Jonathan F Smith

Nathaniel Stephen Wang

Sergey A Dryga

Delbert Linn Harris

John Dustin Loy

Lyric Colleen Bartholomay

Ed Scura

Parinaz Aliahmad

Martina Felderman

Ian Caley

Maureen Maughan

Vernon McNeil Coffield, Iii

Nancy C Carrico

Jason L Dehart

Robert Christopher Brown

Jon O Rayner

Jonathan O Rayner

Maureen F Maughan

Shigeki Miyake-Stoner

Maung Nyan Win

Jason DeHart

Harold Alterson

Matthew Erdman

Kim Butler

Jonathan Fowler Smith

Ian J Caley

Kim Alterson

Vernon Mcneil Coffield Iii

The present disclosure generally relates to viral-based expression systems suitable for the production of molecule of interests in recombinant host cells. The disclosure particularly relates to nucleic acid constructs, such as expression vectors, containing a modified arterivirus genome or replicon RNA in which at least some of its original viral sequence has been deleted. Also included in the disclosure are viral-based expression vectors including one or more expression cassettes encoding heterologous polypeptides. In some embodiments, the expression cassettes are configured and positioned at defined locations on the viral genome so as to enable expression of the heterologous polypeptides in a tunable manner.

Recombinant arterivirus replicon systems and uses thereof

The invention provides RNA replicons useful for administering a heterologous protein or peptide into a mammal and eliciting a reduced immune response or no immune response from the mammal. The RNA replicons have RNA sequences encoding for a heterologous protein or peptide, New World alphavirus nonstructural proteins nsP1, nsP2, and nsP4; and an alphavirus nsP3 protein macro domain, central domain, and hypervariable domain. The encoded hypervariable domain can have an amino acid sequence derived from an Old World alphavirus nsP3 hypervariable domain; or can have an amino acid sequence derived from a portion of a New World alphavirus nsP3 hypervariable domain, and another portion derived from an Old World alphavirus nsP3 hypervariable domain.

Alphavirus-based replicons for administration of biotherapeutics

The present disclosure generally relates to nucleic acid molecules for use in regulating gene expression. Disclosed herein include nucleic acid molecules containing one or more structural elements of the viral capsid enhancer operably linked to a coding sequence of a gene of interest. In some embodiments, the viral capsid enhancer comprises a Downstream Loop (DLP) from a viral capsid protein, or a variant of the DLP.

Compositions and methods for enhancing gene expression

The present disclosure generally relates to the use of different self-amplifying RNA molecules to enhance immune responses, for example immune responses following prophylactic vaccination or therapeutic administration. Some embodiments relate to compositions and methods for inducing an immune response in a subject using prime-boost immunization regimens.

Induce and enhance immune responses using recombinant replicon systems

The present disclosure generally relates to viral-based expression systems suitable for the production of molecules of interest. The disclosure relates to nucleic acid constructs, such as expression vectors, containing a modified replicon RNA which includes a modified 5'-unstranslated region (5&#x2032;-UTR) and, optionally, at least some of its original viral sequence encoding structural proteins having been deleted. Also disclosed are methods for producing polypeptides of interest.

Recombinant virus replicon systems and uses thereof

Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector of replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Use of microRNAs to control virus helper nucleic acids

The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) encoding heterologous proteins, which can be useful for various therapeutic purposes as well as for the production of desired proteins. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that encodes a heterologous protein. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs (or DNA or RNA molecules) of the invention to an organism provides for therapeutic benefits as well as for the production of desired proteins.

Recombinant RNA particles and methods of producing proteins

The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) targeting pathogen sequences, which can be useful as an RNA vaccine. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that binds to a target sequence of a pathogenic organism. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs of the invention to an organism provides a protection to the organism from the pathogen.

Recombinant RNA particles and methods of use

A method of quickly producing a vaccine for a biotype of pathogenic microorganism is described, where a nucleic acid molecule or fragment thereof is obtained from a biological sample from an animal exposed to the microorganism, a protective molecule is prepared based on the nucleic acid molecule of interest or fragment thereof, and administered to an animal which has been or is as risk of being exposed to the microorganism. A protective response to the biotype of the microorganism is obtained in the animal.

Method of rapidly producing improved vaccines for animals

Compositions and methods of protecting aquatic invertebrates from disease is shown. In one embodiment, dsRNA or antisense RNA to a nucleic acid molecule of the disease-causing microorganism is prepared and delivered to the animal. In another embodiment, a nucleic acid molecule of the disease-causing microorganism is delivered to the animal. In another embodiment, the RNA or nucleic acid molecule is delivered to the animal by replicon particle. In a further embodiment, the protective molecule is delivered to the digestive tract of the animal. Protection from disease is obtained.

Methods and compositions to protect aquatic invertebrates from disease

Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Growing community of inventors

Apex, NC, United States of America

Kurt Iver Kamrud