Methods and devices related to controlled delivery of phages as a theranostic tool
Inventors
Assignees
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Publication Number
US-11667895-B2
Publication Date
2023-06-06
Expiration Date
Abstract
Disclosed herein is an engineered bacteriophage comprising an indicator gene, wherein said indicator gene is an RNA aptamer or a green fluorescent protein (GFP) or GFP-like protein, and further wherein said indicator gene can indicate the presence of a microorganism, such as a bacterial infection. The engineered bacteriophage can be capable of infecting and killing the microorganism. The engineered microorganism can be in a composition for delivery to a subject, and can be in hyaluronic acid, for example. Also disclosed are methods of using the engineered bacteriophage to diagnose and/or treat a subject with a bacterial infection.
Core Innovation
The invention relates to an engineered lytic staphylococcal bacteriophage that comprises an indicator gene. The indicator gene is an RNA aptamer and indicates a presence of a target of interest. The indicator behavior provides detection by using the RNA aptamer to report interaction that is read as fluorescence.
In representative implementations, the RNA aptamer is an aptamer such as Spinach or a derivative, and the indication is fluorescence associated with interaction between the RNA aptamer and a GFP-like fluorophore. The GFP-like fluorophore is a molecule selected from DFHBI, DMHBI, DMABI, or 2-HBI, enabling fluorescence reporting when the corresponding molecule is present.
The invention also provides a composition including hyaluronic acid that encapsulates the engineered bacteriophage. The hyaluronic acid is provided as a crosslinked hyaluronic acid hydrogel scaffold and is described as enabling triggered release of the engineered bacteriophages when the composition contacts the target of interest. This enables simultaneous detection and treatment associated with phage infecting and killing activity for the target of interest.
Claims Coverage
The independent claim set includes two independent claims. Claim 1 is directed to an engineered lytic staphylococcal bacteriophage with an RNA aptamer indicator gene, and claim 8 is directed to a composition comprising that bacteriophage encapsulated in hyaluronic acid.
Engineered lytic staphylococcal bacteriophage with RNA aptamer indicator gene
An engineered lytic staphylococcal bacteriophage comprising an indicator gene, wherein the indicator gene is an RNA aptamer, and further wherein the indicator gene can indicate a presence of a target of interest.
Encapsulated engineered lytic staphylococcal bacteriophage in hyaluronic acid
A composition comprising an engineered lytic staphylococcal bacteriophage comprising an indicator gene, wherein the indicator gene is an RNA aptamer, and further wherein the indicator gene can indicate presence of a target of interest; and hyaluronic acid, wherein the engineered bacteriophage is encapsulated within the hyaluronic acid.
Overall, the claims cover an engineered lytic staphylococcal bacteriophage that includes an RNA aptamer indicator gene for indicating a presence of a target of interest, and a composition where the engineered bacteriophage is encapsulated within hyaluronic acid to enable target-linked release.
Stated Advantages
Enables detection by fluorescence.
Enables triggered release of the engineered bacteriophages when the composition contacts the target of interest.
Enables simultaneous detection and treatment associated with phage infecting and killing activity for the target of interest.
Documented Applications
Detection of a target of interest.
Treatment associated with phage infecting and killing activity for the target of interest.
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