Multigenome retroviral vector preparations and methods and systems for producing and using same
Inventors
Ter Meulen, Jan Henrik • BERGLUND, Peter Lars Aksel
Assignees
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Publication Number
US-10179919-B2
Publication Date
2019-01-15
Expiration Date
Abstract
The present invention provides novel multigenome retroviral vectors, methods and packaging systems for making such retroviral vectors and methods of use.
Core Innovation
The invention relates to a recombinant multigenome retroviral vector preparation comprising multiple retroviral particles that deliver different sequences of interest. The preparation comprises particles having two copies of first and second retroviral vector genomes, particles having one copy of each of two different retroviral vector genomes, and particle types that include one copy of the first or second genome together with one copy of the third genome, wherein the first, second and third sequences of interest are different.
The retroviral vector preparation is pseudotyped with a heterologous envelope glycoprotein. The packaging system uses separate nucleic acid molecules for an envelope protein, gag and pol proteins, and rev, and includes nucleic acid molecules carrying first, second and third retroviral vector genomes comprising different sequences of interest, optionally vpx, in a packaging cell or cell line.
The invention further provides a multigenome retroviral vector packaging system including at least three nucleic acid molecules each comprising a retroviral vector genome with a unique sequence of interest, together with one or more nucleic acid molecules encoding components necessary to generate pseudotyped retroviral vector particles. The described embodiments include lentiviral embodiments and control of relative input ratios among genome-encoding nucleic acids to generate the multigenome retroviral vector preparation.
Claims Coverage
The document includes three independent claims. Across the independent claims, the inventive coverage focuses on multigenome particle composition delivering different sequences of interest, pseudotyping with a heterologous envelope glycoprotein via dedicated packaging components, and a multigenome packaging system architecture with optional vpx and a packaging cell line.
Multigenome particle composition delivering different sequences of interest
A recombinant multigenome retroviral vector preparation comprising multiple retroviral particles with different retroviral vector genome combinations and different sequences of interest, wherein the first, second and third sequences of interest are different.
Pseudotyping with a heterologous envelope glycoprotein
The retroviral vector preparation of the multigenome particle composition is pseudotyped with a heterologous envelope glycoprotein.
Packaging system with separate nucleic acids for envelope, gag/pol, rev, and multiple genomes
A retroviral vector packaging system comprising separate nucleic acid molecules for an envelope protein, gag and pol proteins, rev, and multiple retroviral vector genomes comprising different sequences of interest, optionally including a nucleic acid molecule encoding vpx, and comprising a packaging cell or cell line.
Multigenome retroviral vector packaging system architecture with optional vpx and packaging cell line
A multigenome retroviral vector packaging system comprising at least three nucleic acid molecules each comprising a retroviral vector genome comprising a unique sequence of interest, one or more nucleic acid molecules encoding components necessary to generate pseudotyped retroviral vector particles, optionally a nucleic acid molecule encoding vpx, and a packaging cell line.
Overall, the claims cover multigenome retroviral vector preparations and corresponding packaging systems defined by multiple genome combinations, pseudotyping with a heterologous envelope glycoprotein, and packaging components including optional vpx and a packaging cell line.
Stated Advantages
Quantitative control of the ratios of homozygous versus heterozygous/reassortant particles.
Outcomes using multigenome versus single-genome multicistronic vectors in mouse models.
Documented Applications
Mouse models.
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