Thursday, July 17, 2025 7/17/2025

A protease-deficient, low mutation rate E. coli for biotherapeutics production

Award Number: R44GM105183
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/27/2012
PERIOD OF PERFORMANCE END DATE: 06/30/2016

Group Awards By:

View Award Description

A protease-deficient, low mutation rate E. coli for biotherapeutics production - DESCRIPTION (provided by applicant): Biotherapeutics is a fast-growth sector in the pharmaceutical market with monoclonal antibodies accounting for almost 50% of the 100 billion USD spent each year on protein therapies. Bacterial fermentation, which accounts for about 35% of all protein therapeutics manufacture, continues to be the most economical method of generating proteins that do not require eukaryotic post-translational modifications. The need for efficient and economical bacterial bioprocessing becomes even more important as products such as single chain antibodies gain traction as inexpensive alternatives to monoclonal antibody therapeutics, which are the most expensive of all drugs. The common industry bacterial strains, however, can be problematic. Unmodified strains suffer from overproduction-induced stress responses that limit stable growth and can cause cell lysis. Further, biologics, such as single-chain antibodies, are often protease-sensitive and difficult to produce in common industry strains. Scarab Genomics' unique production platform Clean Genome(R) E. coli was engineered by genomic modifications to the K-12 strain MG1655, eliminating unwanted or unnecessary DNA including mobile insertion elements and prophage. Other deletions were designed to eliminate noxious sequences that can limit their productivity in bioprocessing, and enhance recombinant protein synthesis and plasmid DNA production. The current application proposes to build on the most advanced Clean Genome strain now incorporating 69 deletions for a 20% genome reduction, by generating from this starting point, a new strain combining a low mutation rate with low protease activity. In Phase I we propose to remove protease genes and error-prone polymerase genes to construct a single strain with these properties. This strain will be tested for its capacity to produce simple proteins and plasmid DNA. In Phase II the genetic background will be further refined by deleting from the genome the 23 remaining stress-induced toxin/antitoxin genes and the quorum-sensing gene luxS. This unique stress-resistant strain will be evaluated for optimal growth and production characteristics including its ability to effectively produce single- chain antibodies and other protease-sensitive proteins. Further, it will be tested for production of plasmids with difficult-to-replicate secondary structure. Finally, to meet commercialization standards, the new strain will be compared with competing industry strains in fed-batch fermentations. When developed, the single all-purpose production strain will greatly simplify the manufacture of biologics such as single-chain antibodies and offer the pharmaceutical industry a tool by which the most difficult but high-value biologics can be made efficiently and cheaply.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2014	SCARAB GENOMICS, LLC	1202 ANN ST	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	3	11/15/2016	NON-COMPETING CONTINUATION	-$95,979
2017	2014	SCARAB GENOMICS, LLC	1202 ANN ST	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	001	3	2/14/2017	NON-COMPETING CONTINUATION	$95,979
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $713,455 )
2014	2014	SCARAB GENOMICS LLC	1202 ANN STREET	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	3	7/28/2014	NON-COMPETING CONTINUATION	$713,455
														Subtotal = $713,455

Issue Date FY: 2013 ( Subtotal = $892,757 )
2013	2013	SCARAB GENOMICS LLC	1202 ANN STREET	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	001	2	8/28/2013	EXTENSION WITH OR WITHOUT FUNDS	$910,959
2013	2012	SCARAB GENOMICS LLC	1202 ANN STREET	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	1	8/21/2013	NEW	-$18,202
														Subtotal = $892,757

Issue Date FY: 2012 ( Subtotal = $155,032 )
2012	2012	SCARAB GENOMICS LLC	1202 ANN STREET	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	1	9/27/2012	NEW	$155,032
														Subtotal = $155,032

Grand Total All Awards = $1,761,244

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A protease-deficient, low mutation rate E. coli for biotherapeutics production

Award Number: R44GM105183

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/27/2012

PERIOD OF PERFORMANCE END DATE: 06/30/2016

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer