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Project Title:  Just in Time Medications from Gastrointestinal Resident Microbial Systems Reduce
Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 04/01/2020  
End Date: 03/31/2022  
Task Last Updated: 01/19/2023 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Langer, Robert  Sc.D. / Massachusetts Institute of Technology 
Address:  Department of Chemical Engineering 
500 Main St, Room 76-661 
Cambridge , MA 02142 
Email: rlanger@mit.edu 
Phone: 617-253-3107  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Massachusetts Institute of Technology 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Traverso, Carlo  Ph.D. Brigham and Women's Hospital 
Project Information: Grant/Contract No. NNX16AO69A-T0504 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Unique ID: 13957 
Solicitation / Funding Source: 2020 TRISH BRASH1901: Translational Research Institute for Space Health (TRISH) Biomedical Research Advances for Space Health 
Grant/Contract No.: NNX16AO69A-T0504 
Project Type: Ground 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Genetically engineered microbes (synthetic microbes) represent a promising approach for the space- and resource-efficient production of active pharmaceutical compounds during long-duration space flight. Microbes are already widely used industrially for the fermentation-based production of many high-value compounds from simple feed stocks. Furthermore, it has been proposed that during long-duration space flight microbes could be stored as small starter stocks and cultured to make fuels, food, and pharmaceuticals. Here we propose to develop an ingestible device that can be used for the modular production of medicines on demand via the use of integrated synthetic microbes.

Research Impact/Earth Benefits: During the entire project period we have developed several key technologies with significant impact beyond this project:

Impact 1: Porous membranes for controlled release of bacteria. We developed a technology to tune the release rate of bacteria. This technology may have application generally for the controlled release of bacteria in therapeutics or other applications were controlled release may be required (e.g. plant probiotics). While there has been extensive work in developing technologies for controlling the release profiles of small molecules from different types of matrices, the technology described here fills a growing need to control the release of bacteria that are intended as therapeutics.

Impact 2: Matrices for dosing and manipulating dry bacteria. Bacteria are traditionally handled as liquid suspensions, slurries or frozen pastes. All these modalities require a dedicated environment (e.g. wet bench laboratory) and expert personnel to handle. In contrast to these, commercially available bacterial pills (i.e. probiotics) present a tantalizing alternative. However, our previously funded Translational Research Institute for Space Health (TRISH) work demonstrated that a many of these commercial products do not have the viabilities promised and some have extremely poor recovery of viable bacteria. The technology developed during this project builds on our previously developed bacterial formulations, expanding them to incorporation of bacteria directly into easily handled matrices. Furthermore, we showed that the bacteria not only can be recovered with high viability but also that maximal enzymatic/metabolic activity is recovered in less than 1 hr. Such a simple medium for manipulating, aliquoting and dosing bacteria may have impacts beyond this project including streamlined manufacturing workflows of components that may use the incorporated bacteria for treating, sensing or controlling down stream components.

Impact 3: Transfer of biosynthetic pathways to probiotic bacteria. In the proposed project we selected target molecules that are currently part of the NASA med kit and which have biosynthetic pathways previously established to differing degrees in bacteria. This strategic choice enhanced the likelihood of success achieving a traditionally challenging goal (i.e., biosynthesis of any molecule) in the abbreviated duration of the project. During this reporting period, we have established these biosynthetic pathways in a probiotic strain with a proven track record for use in humans. These strains may have impacts beyond this project by demonstrating and defining the challenges of biosynthesizing Food and Drug Administration (FDA) approved molecules in probiotic strains which are being actively used by commercial entities seeking FDA approval for microbial therapeutics.

Impact 4: Ingestible micro-fermenter capsules. During this project we developed a prototype micro-fermenter capsule and validated its function and safety in a large animal model. This device may have applications generally for the rapid production of therapies on demand in low resource environments on earth. These devices may be of used to rapidly produce microbial medicines at the point of care without the need for traditional microbial culturing equipment or training.

Task Progress & Bibliography Information FY2022 
Task Progress: Genetically engineered microbes (synthetic microbes) represent a promising approach for the space- and resource-efficient production of active pharmaceutical compounds during long-duration spaceflight. Microbes are already widely used industrially for the fermentation-based production of many high-value compounds from simple feed stocks. Furthermore, it has been proposed that during long-duration spaceflight microbes could be stored as small starter stocks and cultured to make fuels, food, and pharmaceuticals. Here, we propose to develop an ingestible device that can be used for the modular production of medicines on demand via the use of integrated synthetic microbes. Specifically, our project aims to provide a countermeasure for a limited pharmacy during exploration space travel by using synthetic microbes to generate medicines just at the time of need, freeing related resources to increase the total variety and potential output of a microbe-based pharmacy.

We developed a proof-of-concept microbial pharmacy as a countermeasure to current limits and lack of flexibility of a traditional pharmacy during exploration missions (i.e., limited doses and stability of medicines). Our microbial pharmacy is made of dry stabilized microbial paper that can be stored in the shape of a book with one medicine per page, and companion ingestible capsules fermenters that allow just-in-time production of a target medicine inside the body from a miniature portion of the microbial paper. None of the components need power nor refrigeration to function. By separating the instructions for making a medicine (i.e., engineered microbial therapeutics) from the generic raw feedstocks (i.e., body heat, nutrients) a microbial pharmacy would allow many more doses of just the right medicine to be made only at the time of need.

Bibliography: Description: (Last Updated: 05/19/2020) 

Show Cumulative Bibliography
 
 None in FY 2022
Project Title:  Just in Time Medications from Gastrointestinal Resident Microbial Systems Reduce
Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 04/01/2020  
End Date: 03/31/2022  
Task Last Updated: 07/22/2021 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Langer, Robert  Sc.D. / Massachusetts Institute of Technology 
Address:  Department of Chemical Engineering 
500 Main St, Room 76-661 
Cambridge , MA 02142 
Email: rlanger@mit.edu 
Phone: 617-253-3107  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Massachusetts Institute of Technology 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Traverso, Carlo  Ph.D. Brigham and Women's Hospital 
Project Information: Grant/Contract No. NNX16AO69A-T0504 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Unique ID: 13957 
Solicitation / Funding Source: 2020 TRISH BRASH1901: Translational Research Institute for Space Health (TRISH) Biomedical Research Advances for Space Health 
Grant/Contract No.: NNX16AO69A-T0504 
Project Type: Ground 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Genetically engineered microbes (synthetic microbes) represent a promising approach for the space- and resource-efficient production of active pharmaceutical compounds during long-duration space flight. Microbes are already widely used industrially for the fermentation-based production of many high-value compounds from simple feed stocks. Furthermore, it has been proposed that during long-duration space flight microbes could be stored as small starter stocks and cultured to make fuels, food, and pharmaceuticals. Here we propose to develop an ingestible device that can be used for the modular production of medicines on demand via the use of integrated synthetic microbes

Research Impact/Earth Benefits: During this reporting period we have developed three key technologies with significant impact beyond this project:

Impact 1: Porous membranes for controlled release of bacteria. We developed a technology to tune the release rate of bacteria. This technology may have application generally for the controlled release of bacteria in therapeutics or other applications where controlled release may be required (e.g., plant probiotics). While there has been extensive work in developing technologies for controlling the release profiles of small molecules from different types of matrices, the technology described here fills a growing need to control the release of bacteria that are intended as therapeutics.

Impact 2: Matrices for dosing and manipulating dry bacteria. Bacteria are traditionally handled as liquid suspensions, slurries, or frozen pastes. All these modalities require a dedicated environment (e.g., wet bench laboratory) and expert personnel to handle. In contrast to these, commercially available bacterial pills (i.e., probiotics) present a tantalizing alternative. However, our previously funded Translational Research Institute for Space Health (TRISH) work demonstrated that many of these commercial products do not have the viabilities promised and some have extremely poor recovery of viable bacteria. The technology developed during this reporting period builds on our previously developed bacterial formulations, expanding them to incorporation of bacteria directly into easily handled matrices. Furthermore, we showed that the bacteria not only can be recovered with high viability but also that maximal enzymatic/metabolic activity is recovered in less than 1 hr. Such a simple medium for manipulating, aliquoting, and dosing bacteria may have impacts beyond this project including streamlined manufacturing workflows of components that may use the incorporated bacteria for treating, sensing, or controlling down stream components.

Impact 3: Transfer of biosynthetic pathways to probiotic bacteria. In the proposed project we selected target molecules that are currently part of the NASA med kit and which have biosynthetic pathways previously established to differing degrees in bacteria. This strategic choice enhanced the likelihood of success achieving a traditionally challenging goal (i.e., biosynthesis of any molecule) in the abbreviated duration of the project. During this reporting period, we have established these biosynthetic pathways in a probiotic strain with a proven track record for use in humans. These strains may have impacts beyond this project by demonstrating and defining the challenges of biosynthesizing Food and Drug Administration (FDA) approved molecules in probiotic strains which are being actively used by commercial entities seeking FDA approval for microbial therapeutics.

Task Progress & Bibliography Information FY2021 
Task Progress: Genetically engineered microbes (synthetic microbes) represent a promising approach for the space- and resource-efficient production of active pharmaceutical compounds during long-duration space flight. Microbes are already widely used industrially for the fermentation-based production of many high-value compounds from simple feed stocks. Furthermore, it has been proposed that during long-duration space flight microbes could be stored as small starter stocks and cultured to make fuels, food, and pharmaceuticals. Here we propose to develop an ingestible device that can be used for the modular production of medicines on demand via the use of integrated synthetic microbes. Specifically, our project aims to provide a countermeasure for a limited pharmacy during exploration space travel by using synthetic microbes to generate medicines just at the time of need freeing related resources to increase the total variety and potential output of a microbe-based pharmacy. Currently, we are generating pharmaceutical-producing microbes as well as an ingestible device compatible with just-in-time medicine production. In the coming year, we will combine these two elements and generate in vitro and in vivo datasets of device and microbe function.

Bibliography: Description: (Last Updated: 05/19/2020) 

Show Cumulative Bibliography
 
 None in FY 2021
Project Title:  Just in Time Medications from Gastrointestinal Resident Microbial Systems Reduce
Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 04/01/2020  
End Date: 03/31/2022  
Task Last Updated: 07/23/2020 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Langer, Robert  Sc.D. / Massachusetts Institute of Technology 
Address:  Department of Chemical Engineering 
500 Main St, Room 76-661 
Cambridge , MA 02142 
Email: rlanger@mit.edu 
Phone: 617-253-3107  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Massachusetts Institute of Technology 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Traverso, Carlo  Ph.D. Massachusetts Institute of Technology 
Project Information: Grant/Contract No. NNX16AO69A-T0504 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Unique ID: 13957 
Solicitation / Funding Source: 2020 TRISH BRASH1901: Translational Research Institute for Space Health (TRISH) Biomedical Research Advances for Space Health 
Grant/Contract No.: NNX16AO69A-T0504 
Project Type: Ground 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Genetically engineered microbes (synthetic microbes) represent a promising approach for the space- and resource-efficient production of active pharmaceutical compounds during long-duration space flight. Microbes are already widely used industrially for the fermentation-based production of many high-value compounds from simple feed stocks. Furthermore, it has been proposed that during long-duration space flight microbes could be stored as small starter stocks and cultured to make fuels, food, and pharmaceuticals. Here we propose to develop an ingestible device that can be used for the modular production of medicines on demand via the use of integrated synthetic microbes.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2020 
Task Progress: New project for FY2020.

Bibliography: Description: (Last Updated: 05/19/2020) 

Show Cumulative Bibliography
 
 None in FY 2020