Polypeptides, nucleic acid molecules, compositions, and related methods
Inventors
MILLAY, Douglas • GAMAGE, Dilani • CHERNOMORDIK, Leonid • LEIKINA, Evgenia
Assignees
Usa REPRESENTED BY SECRETARY Department Of Hhs AS • Cincinnati Childrens Hospital Medical Center • US Department of Health and Human Services
Publication Number
US-12054526-B2
Publication Date
2024-08-06
Expiration Date
2039-06-14
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Abstract
Some embodiments of the invention include polypeptides comprising a myomerger polypeptide or an extracellular myomerger polypeptide. Other embodiments of the invention include nucleic acid molecules encoding polypeptides comprising a myomerger polypeptide or an extracellular myomerger polypeptide. Other embodiments of the invention include vectors comprising the nucleic acid molecule. Yet other embodiments of the invention include methods of using a myomerger polypeptide or an extracellular myomerger polypeptide. Additional embodiments of the invention are also discussed herein.
Core Innovation
The invention relates to polypeptides comprising a myomerger polypeptide or an extracellular myomerger polypeptide, nucleic acid molecules encoding these polypeptides, vectors containing such nucleic acids, and methods of using myomerger polypeptides. These polypeptides, nucleic acids, and related compositions are designed to promote membrane fusion, increase membrane permeability, form pores, stress membranes, or lyse cells and liposomes.
The problem addressed by the invention is the need for additional methods to increase cell membrane permeability, which can assist in treating diseases such as infections. Known molecules and methods exist, but further solutions are desired to enhance membrane permeability and affect membrane fusion processes.
The invention distinguishes the roles of Myomaker and Myomerger proteins in the fusion process, showing that myomerger polypeptides or their extracellular domains can stress membranes, induce pore formation, and promote fusion completion independently of Myomaker. The invention provides compositions and methods that include polypeptides and nucleic acids coding for myomerger proteins or extracellular domains thereof, and demonstrates their use in increasing membrane permeability or inducing cell or liposome lysis, with applications in various cell types including bacterial, mammalian, and cancer cells.
Claims Coverage
The patent discloses one independent claim focused on a method of lysing a liposome or cell by contacting it with an isolated extracellular myomerger polypeptide or related compositions, excluding myomaker polypeptides.
Method for lysing liposomes or cells using extracellular myomerger polypeptides
A method comprising contacting a liposome or animal or bacterial cell with an isolated extracellular myomerger polypeptide selected from SEQ ID NOs: 19-24, or a composition including such polypeptides or nucleic acids encoding them, resulting in lysis of the liposome or cell, wherein the composition excludes myomaker polypeptide or its encoding nucleic acids.
Specific targeting of diverse cell types including mammalian, bacterial, and cancer cells
The method includes lysis of mammalian cells, bacterial cells (gram-positive or gram-negative), cancer cells including tumor cells, indicating broad applicability of the extracellular myomerger polypeptide without requiring myomaker expression.
Modes of administration and application conditions
Contacting can occur in vitro or in vivo, including by injection, with resulting formation of pores in cell or liposome membranes and subsequent lysis.
Composition concentration and formulation
The extracellular myomerger polypeptide, nucleic acid molecule, or vector can be present in compositions in amounts ranging from about 0.0001% to about 99% by weight, and compositions can be pharmaceutical compositions suitable for various administration routes.
The claims focus on methods of lysing cells or liposomes via extracellular myomerger polypeptides or their encoding nucleic acids, emphasizing the capacity to act independently of myomaker polypeptides, effective on a range of cell types including cancer and bacterial cells, with various administration modes and pharmaceutical formulations.
Stated Advantages
The invention provides improved methods to increase membrane permeability and induce membrane fusion or lysis, offering enhanced treatment approaches for diseases such as infections.
Myomerger polypeptides function independently of Myomaker, providing a novel stepwise mechanism for membrane fusion and pore formation.
The extracellular myomerger polypeptide can be used as a functional agent to permeabilize membranes, stress membranes, form pores, and lyse cells or liposomes.
Documented Applications
Methods of using myomerger polypeptides or extracellular myomerger polypeptides to increase membrane permeability of cells or liposomes for purposes including pore formation and cell or liposome lysis.
Contacting bacterial cells (gram-positive and gram-negative), fungal cells, insect cells, animal cells including mammalian and muscle cells, and cancer cells to promote fusion or induce lysis.
Therapeutic applications involving treating bacterial infections, fungal infections, and cancers by lysing cells or increasing membrane permeability.
Use in pharmaceutical compositions suitable for administration via topical, subcutaneous, intravenous, intramuscular, and various other routes.
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