Compositions and methods for therapeutic or vaccine delivery
Inventors
FISCHER-LOUGHEED, Jacqueline • STEELE, Bradford H. • Roh, Cecilia • Johnson, Robert G.
Assignees
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Publication Number
US-11992524-B2
Publication Date
2024-05-28
Expiration Date
Abstract
Described herein are compositions for delivering a therapeutic or vaccine. Also described herein are methods for using the compositions described herein for delivering a therapeutic or a vaccine.
Core Innovation
The invention relates to a recombinant retroviral vector, specifically a recombinant murine leukemia virus (MLV), engineered to have defective retroviral integration activity by using a mutant integrase. The mutant integrase includes at least one mutation in an Mg2+ binding motif of a catalytic core domain, selected from D125A, D184A, and E220A (and combinations), and the defective integration activity disables retroviral integration while retaining vector performance such that the payload is expressed in the subject.
The recombinant vector is used to treat or prevent a disease or condition in a subject by administering a recombinant retroviral vector comprising a first nucleic acid sequence encoding the mutant integrase and a second nucleic acid sequence encoding at least one payload. The payload comprises an antigen, and the antigen induces an immune response in the subject, thereby treating or preventing the disease or condition. The at least one payload is expressed in the subject for at least three days.
The disclosed system further provides functional outcomes consistent with defective integration activity: payload expression decreases over time due to lack of integration, while secreted antigen proteins are detected. The document also describes antigen and targeting variants, including pathogen polypeptides and cancer polypeptides, and antigen embodiments such as SARS-CoV-2 Spike variants and influenza antigens. Additionally, the disclosed retroviral envelopes include modifications for targeting, such as a Sindbis E2 protein E160G to target dendritic cells, and optional modified untranslated region (UTR) elements to enhance payload expression.
Claims Coverage
The independent claims cover an MLV-based recombinant retroviral vector with defective integration activity driven by Mg2+ binding motif integrase mutations (D125A, D184A, and/or E220A) and an antigen payload that expresses for at least three days to induce an immune response. The main inventive features are the mutant integrase, the antigen payload, and the specified expression duration and vector identity.
Mg2+ binding motif mutant integrase for defective integration
A recombinant murine leukemia virus (MLV) retroviral vector comprising a mutant integrase in which, compared to a wild-type integrase, the mutant integrase comprises at least one mutation in a Mg2+ binding motif of a catalytic core domain selected from D125A, D184A, and E220A, wherein the recombinant retroviral vector has defective retroviral integration activity as compared to a recombinant retroviral vector comprising the wild-type integrase.
Antigen payload inducing an immune response
The recombinant retroviral vector comprises at least one payload comprising an antigen, wherein the at least one payload is expressed in the subject for at least three days, and wherein the antigen induces an immune response in the subject, thereby treating or preventing the disease or condition in the subject.
Method of treating or preventing a disease using the engineered MLV vector
A method of treating or preventing a disease or condition in a subject by administration of a recombinant retroviral vector with defective retroviral integration activity, comprising administering to the subject a recombinant retroviral vector comprising a first nucleic acid sequence encoding the mutant integrase and a second nucleic acid sequence encoding the at least one payload comprising an antigen.
Across the independent claims, coverage centers on administering an MLV recombinant retroviral vector with defective retroviral integration activity caused by Mg2+ binding motif catalytic core integrase mutations (D125A/D184A/E220A) together with an antigen payload. The antigen is expressed in the subject for at least three days and induces an immune response that treats or prevents the disease or condition.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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