Modular betaretrovirus receptor attachment and cell entry proteins
OwnerWelkin E. Johnson, Laura R. Hall +2inventors
InventorsWelkin E. Johnson, Laura R. Hall, Casey Roberts, Zachary Williams
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Abstract
The disclosure relates to betaretroviruses (genus Betaretrovirus), and recombinant betaretroviral envelope (rENV) protein for use in viral vector platforms, an engineered delivery vehicle and gene therapy, their associated methods of use and manufacture. In particular, the present disclosure provides compositions and methods to tune betavirus envelope proteins such that they target a particular cell surface receptor; i.e., are cell and/or tissue-type specific, allowing for better site-specific transgene delivery and expression.
Claims46
A nucleic acid comprising a polynucleotide encoding a transcription unit for a recombinant betaretroviral envelope (rENV) protein comprising a receptor binding domain (RBD), a betaretrovirus surface subunit (SU) domain, and a betaretrovirus transmembrane (TM) domain.
An engineered delivery vehicle comprising (i) a polynucleotide encoding one or more recombinant betaretroviral envelope (rENV) proteins including a receptor binding domain (RBD), a betaretrovirus surface subunit (SU) domain, and a betaretrovirus transmembrane (TM) domain, (ii) a rENV protein including a receptor binding domain (RBD), a betaretrovirus surface subunit (SU) domain, and a betaretrovirus transmembrane (TM) domain, or (iii) both.
An engineered delivery vehicle that comprises a virus-like particle having a recombinant betaretroviral envelope (rENV) protein on its surface, and including a packaged nucleic acid viral vector payload, wherein the rENV protein comprises a receptor binding domain (RBD), a betaretrovirus surface subunit (SU) domain, and a betaretrovirus transmembrane (TM) domain.
A method of forming an engineered delivery vehicle comprising the steps of:
- contacting a target cell and/or a target tissue with a nucleic acid including (i) a polynucleotide encoding one or more recombinant betaretroviral envelope (rENV) proteins having a receptor binding domain (RBD), a betaretrovirus surface subunit (SU) domain, and a betaretrovirus transmembrane (TM) domain, and (ii) at lease one additional polynucleotide including a transcription unit encoding a protein,
- wherein the RBD binds a receptor of interest and wherein expression of the one or more rENV proteins by the target cell and/or the target tissue forms an engineered delivery vehicle including rENV proteins on its surface, and wherein the delivery vehicle includes a payload comprising the at least one additional polynucleotide encoding a protein.
Dependencies are inferred from the claim text.