Cost-Effective Manufacturing of Human Quality mRNA

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$122,108.00
Award Year:
2004
Program:
SBIR
Phase:
Phase I
Contract:
1R43GM070156-01
Award Id:
71641
Agency Tracking Number:
GM070156
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
2130 WOODWARD STREET, AUSTIN, TX, 78744
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
EMMANUELLABOURIER
(512) 651-0200
ELABOURIER@AMBION.COM
Business Contact:
RIGOVALLEJO
(512) 651-0200
RVALLEJO@AMBION.COM
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): The overall objective of this proposal is to develop methods for the cost-effective, large-scale synthesis (up to kilograms amounts) of capped RNA. Companies such as Wyeth Vaccines, AlphaVax and Merix Biosciences are using capped RNA to produce human vaccines against cancers and infectious diseases such as HIV and biowarfare agents. The mMESSAGEmMACHINE(r) kit, based on Ambion's patented technology, provides the customer with high-yielding transcription reactions for the synthesis of capped RNA. Although this technology is the best available on the market for producing capped RNA, the cost of making capped RNA using this technology under cGMP conditions may be too cost prohibitive to make these RNA-based vaccine strategies commercially feasible. Additionally, the current technology produces a mixture of uncapped, correctly capped and "reverse" capped RNA. Our goals are to decrease the cost of the capped RNA required per human subject by at least 100-fold, to increase the purity of the capped RNA such that >90% of the RNA is correctly capped and to develop methods for assessing the purity of the final RNA product. By developing a new reaction system, we could theoretically increase the yield of these reactions by as much a 8-fold. Preliminary experiments increased the yield up to 3-fold based on this novel strategy. By increasing the ratio of the cap analog to GTP concentrations in these reaction systems, we should be able to increase the percentage of capped RNA in a reaction to 90% and further, by using a novel "anti-reverse cap analog" we will incorporate all of the cap in the correct, functional orientation. Increasing the resistance of the capped RNA to nucleases is one strategy to decrease the amount of RNA required per human subject and we will test various strategies for increasing the stability of the capped RNA in a cell while maintaining its translational competency. Finally, not all of the transcription components required for generating maximum yields are available as an FDA approved component. These proteins will be cloned and expressed in systems approved by the FDA.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government