Recombinant Human Gelatin

Limitations of Animal-Derived Gelatins

Historically, gelatin is produced by extraction from collagen-rich tissues, such as bovine or porcine skin or bone, using either acid or base. Currently available gelatin preparations consist of a distribution of polypeptide fragments of different sizes, different isoelectric points (pI), and different gelling properties, and often exhibit lot-to-lot variability. The physiochemical properties of these gelatins vary depending on method of extraction, amount of thermal denaturation employed, electrolyte content, and, in the case of liquid formulations of vaccines and biologics, the additional processing steps applied to prevent gelling of the resulting material. The variable nature of such gelatin preparations presents a significant challenge to those who use these protein mixtures in the manufacture of gelatin-containing products.

Advantages of Recombinant Human Gelatins

Using recombinant technology, FibroGen produces highly purified, fully characterized, genetically distinct molecules of recombinant human (rh) gelatin designed to be gelling or non-gelling.1,2 FibroGen can design and express rh gelatin molecules with predetermined characteristics, i.e., defined molecular weights and pI, in order to confer specific performance characteristics to match the need in a variety of pharmaceutical applications. Each lot is a homogenous preparation, which can be reproduced in a consistent manner with 99% purity. FibroGen's production system does not contain human or animal components, thereby eliminating the risk of contamination with disease causing pathogens, such as viruses and prions that cause mad cow disease and its human variant Creutzfeldt-Jakob Disease associated with use of animal- and plasma-derived materials. The risk of eliciting an immune response is also reduced as rh gelatin molecules are based on human DNA sequences.

Development Opportunities: Vaccine/Biologic Stabilizer3-5

FibroGen produces FG-5009, a low molecular weight (8.5 kDa) rh gelatin molecule optimized for use as a stabilizing component in vaccine and biologic formulations. Working with leaders in the vaccine market, FibroGen has tested the ability of FG-5009 to stabilize several live attenuated viral vaccines. In vitro stabilization studies have demonstrated that rh gelatin is equivalent to the animal-derived gelatin stabilizer in commercially available vaccines. FibroGen is currently working with customers on formulation development and testing FG-5009 as a stabilizer for other biopharmaceuticals and as an alternative to human serum albumin. FG-5009 was found well tolerated in a safety study of healthy human volunteers, and no significant trends in antibody titers or standard serum chemistry parameters were observed. Research-grade material is available for purchase (please visit our Reagent Store). For more information or a data package on FG-5009, please contact our Business Development group at FibroGen: or (415) 978-1280.

Capsule Gelatin Research and Development Program

FibroGen is conducting research to develop a cost-effective, scalable, plant-based system for the co-production of recombinant proteins for medical and pharmaceutical uses and traditional agricultural products not for human consumption (e.g., ethanol as a gasoline additive and corn oil for lubricants in motor vehicles). The sale of current agricultural products from a recombinant gelatin production crop could drive the marginal cost of recombinant gelatin production near to zero, allowing for direct competition with animal-based gelatins. FibroGen is initiating feasibility studies with major capsule manufacturers to evaluate the suitability of recombinant gelatin for use in their manufacturing systems.

FibroGen has produced a series of recombinant fragments by cloning and expressing defined segments of the human alpha1 (I) procollagen gene. Each bar in the diagram represents a different recombinant gelatin fragment and relative location of the fragment within the helical domain of the human alpha1 (I) chain; similarly colored bars share the same N-terminal sequence. The numbers within each bar represent the number of amino acids in the fragment.

FibroGen's recombinant gelatin molecules analyzed by SDS-PAGE. Each band represents a single molecular weight species of recombinant gelatin secreted into conditioned media by Pichia pastoris strains expressing various collagen fragments. The numbers above each band represent the number of amino acids in the fragment. The left lane shows molecular weight standards (kd) for comparison


  1. Olsen, D. et al. (2005) Expression and characterization of a low molecular weight recombinant human gelatin: development of a substitute for animal-derived gelatin with superior features. Protein Expression and Purification 40:346-357.
  2. Olsen, D. et al. (2003) Recombinant collagen and gelatin for drug delivery. Advanced Drug Delivery Reviews 55:1547-1567.
  3. Liska, V. et al. (2007) Evaluation of a recombinant human gelatin as a substitute for a hydrolyzed porcine gelatin in a refrigerator-stable OKA/Merck live varicella vaccine. Journal of Immune Based Therapies and Vaccines 5:4
  4. Thyagarajapuram, N. et al. (2007) The structure, stability, and complex behavior of recombinant human gelatins. J Pharm Sci 96(12):3363-78.
  5. Thyagarajapuram, N. et al. (2007) Stabilization of proteins by recombinant human gelatins. J Pharm Sci 96(12):3304-15.