Recombinant host cell with heterologous nucleic acids encoding SHREK proteins
Inventors
Wu, Yuntao • DABBAGH, Deemah • He, Sijia • Hetrick, Brian
Assignees
Publication Number
US-12048741-B2
Publication Date
2024-07-30
Expiration Date
2040-09-24
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Abstract
Recombinant viruses include one or more SHREK proteins and are thereby rendered non-infective and can be safely used in vaccines, e.g. to treat or prevent infections and to eliminate e.g. latent virus reservoirs.
Core Innovation
This invention identifies and utilizes a group of mucin-like glycoproteins, termed the SHREK (Surface-Hinged, Rigidly-Extended Killer) family, which are normally found on cell surfaces and act as restriction factors for a range of viruses. When SHREK proteins are expressed in virion-producing cells, they incorporate into assembling virions, thereby attenuating the virus and rendering it non-infective. Such attenuated viruses can be safely used in vaccines to treat or prevent infections and to target latent virus reservoirs.
The patent solves the problem of developing effective antiviral agents and vaccines, specifically addressing the significant health burdens caused by diseases such as COVID-19 and HIV. Current therapeutic options, such as antiretroviral therapy for HIV, require lifelong administration and do not clear latent viral reservoirs. There is also a lack of effective vaccines for certain viruses, highlighting the need for new approaches.
The invention includes recombinant host cells comprising heterologous nucleic acid sequences encoding one or more SHREK proteins and a selected viral genome. This strategy enables the production of attenuated viruses, which can serve as the active components of vaccines. In addition, the SHREK proteins or their extracellular domains can be conjugated to antibodies, creating agents that target and inactivate infectious viral particles.
Claims Coverage
The patent contains two independent claims that define the main inventive features regarding recombinant host cells and methods for producing virions using SHREK proteins and viral genomes.
Recombinant host cell comprising SHREK protein and viral genome
A recombinant host cell includes one or more vectors comprising heterologous nucleic acid sequences encoding one or more SHREK proteins selected from the group consisting of CD43, TMEM123, CD164, Tim-1, CD34, PODXL2, CD45, CD44, Madcam1, glycam1, Cd68, CD148, CX3CL1, CD107a, CD99, and CD7, and a viral genome selected from the group consisting of coronavirus, a lentivirus, a hepadnavirus, and an influenza virus.
Method for producing virions comprising SHREK protein
The method comprises: 1. Introducing into a host cell a nucleic acid sequence encoding at least one SHREK protein (from the specified group) and one or more nucleic acid sequences encoding a viral genome; 2. Culturing the host cell under conditions that permit over-expression of the SHREK protein and viral proteins/nucleic acids, as well as assembly of viral and SHREK components into virions; 3. Recovering the virions from the culture medium.
These inventive features define the creation and use of recombinant host cells containing both SHREK protein-encoding sequences and viral genomes to generate attenuated virions and methods for their production.
Stated Advantages
SHREK proteins, when incorporated into assembling virions, render the virus non-infective, enabling the safe development of attenuated vaccines.
Use of SHREK proteins allows the targeting and elimination of latent virus reservoirs, providing approaches not addressed by existing antiviral therapies.
SHREK-based attenuation does not rely on chemical or conventional biological inactivation, potentially improving vaccine safety and efficacy.
Broad antiviral activity is achieved, as SHREK proteins target multiple enveloped viruses including HIV, SARS-CoV-2, Influenza A, and HBV.
Documented Applications
Attenuated virions comprising SHREK proteins are used as vaccines to treat or prevent infections caused by enveloped viruses such as coronaviruses (including SARS-CoV-2), lentiviruses (including HIV-1), hepadnaviruses (including HBV), and influenza viruses.
SHREK-expressing host cells and cell lines are utilized for the production of attenuated viruses suitable for use in pharmaceutical compositions.
SHREK proteins or SHREK-antibody conjugates are used to treat or prevent viral infections and to eliminate latent virus reservoirs in subjects.
The technology is applicable for both human and veterinary prevention or treatment of diseases caused by enveloped viruses.
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