Cost-Effective Manufacturing of Pharmaceutical mRNA

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44GM070156-02
Agency Tracking Number: GM070156
Amount: $1,075,530.00
Phase: Phase II
Program: SBIR
Awards Year: 2005
Solicitation Year: 2005
Solicitation Topic Code: N/A
Solicitation Number: PHS2005-2
Small Business Information
Ambion, Inc., 2130 Woodward Street, Austin, TX, 78744
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (512) 651-0200
Business Contact
Phone: (512) 651-0200
Research Institution
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, polyadenylated RNA. Several companies are using capped RNA to produce human vaccines against cancers and infectious diseases such as HIV and biowarfare agents. Ambion's patented mMESSAGEmMACHINE(r) kit provides high-yielding transcription reactions for the synthesis of capped RNA. Although this is the best available technology, the costs of producing capped RNA for therapeutic purposes in accordance to the FDA Quality System Requirement (21 CFR, Part 820) are too high for commercial viability. Our objective is to reduce the manufacturing costs such that the use of capped RNA for vaccine development and other therapeutic applications is economically feasible. Our specific aims are: 1. Increase the functional unit activity (purity, homogeneity, orientation) of capped RNA. 2. Decrease the overall cost of capped RNA manufacturing. In Phase I, we 1) developed a batch-fed transcription system that increased the RNA yield by 5-fold, 2) enhanced capped RNA unit activity by producing greater than 80% properly oriented caps, 3) improved the template DNA removal step, 4) produced two key reaction components in animal-free systems, and 5) reduced the cost per dose by -10-fold. For Phase II, we will build on this success by further optimizing the reaction and reducing production costs. We will design and test a reactor for large-scale reactions that allows continuous monitoring and adjusting of the relevant components of the reaction. We will also investigate new cap analogs and optimize RNA polyadenylation and purification to both reduce costs and improve unit activity. Finally, we will manufacture FDA-compliant enzymes and reagents to synthesize capped RNA at a lower cost. Based on our prior success, we believe we can further decrease the costs to approximately $10/dose for human use, and thereby enable the development of RNA-based vaccines for existing and emerging pathogens.

* Information listed above is at the time of submission. *

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