A startup focused on developing enhanced protein therapeutics based on computational protein design and synthetic biology technologies—whose cofounders include George M. Church, Ph.D.—has emerged from stealth mode, winning $2.1 million in seed funding.
GRO Biosciences said it would use the seed funding to support the buildout of bioprocess development for its platform of genomically recoded bacteria for producing therapeutic proteins with enhanced properties—including increased potency and stability and improved targeting and delivery into cells and tissues.
By recoding the genomes of bacterial strains used in biologics production, GRO Biosciences reasons that it can expand beyond the 20 amino acid building blocks typically found in proteins to introduce nonstandard amino acids that can customize the shape and chemical properties of the protein.
“GRO Biosciences' technology addresses the fundamental limitations of producing proteins with nonstandard amino acids, opening up the possibility of creating a new universe of designer proteins with enhanced therapeutic properties at commercial scale,” Dr. Church, professor of genetics at Harvard Medical School and head of the company's scientific advisory board, said in a statement.
The company says its technology is designed to address a key challenge of therapeutic proteins—instability. Many such proteins, including nearly all monoclonal antibodies, maintain their 3D structure with disulfide bonds. Yet these bonds are not stable in the presence of reducing agents found in cells and in blood, resulting in a short-lived therapeutic effect after the proteins are administered to patients.
GRO Biosciences has developed a recoded strain of bacteria that replaces all UAG stop codons with UAA stop codons and reprograms the UAG codon to new amino acids such as selenocysteine. UAG and UAA are two of three stop codons responsible for halting the elongation of a growing protein; the other is UGA. By replacing all codons that code for cysteine residues in a protein with UAG, selenocysteine can be selectively incorporated in place of cysteine residues to form stabilizing diselenide bonds.
GRO Biosciences says it can extend the half-life of therapeutic proteins by replacing disulfide bond–forming cysteine amino acid residues with selenocysteine, a naturally occurring amino acid found in the cell, yet rarely incorporated into proteins. Selenocysteine has a structure and chemical properties very similar to cysteine; however, diselenide bonds are stable under the same conditions, unlike disulfide bonds.
Preliminary Proof of Concept
The company said it has established preliminary proof of concept of its platform by producing diselenide-stabilized antibody products as well as therapeutic proteins, including human growth hormone, in its selenocysteine recoded bacteria.
In all instances, according to GRO Biosciences, yields were high, selenocysteine incorporation at the desired sites was 100%, and all diselenide bonds formed correctly, leading to the properly folded protein. The diselenide bonds dramatically increased stability in physiologically relevant conditions, as confirmed by functional assays, the company added.
Last year, Dr. Church led a research team in applying recoding to design and synthesize a bacterial genome, an exercise designed to show how new organisms could be created that feature functionality not previously seen in nature.
Digitalis Ventures led the seed funding, with participation from Innovation Endeavors, the venture capital firm whose co-founders include Eric Schmidt, executive chairman of Google’s parent company Alphabet Inc.
“Protein therapeutics represent a $180 billion market, yet product stability, targeting, and delivery into the cell still remain significant challenges to be addressed if we are to enhance the patient experience, achieve better compliance and improve health outcomes,” said Geoffrey W. Smith, founder and managing partner of Digitalis Ventures.
GRO Biosciences is one of numerous companies founded by Dr. Church; others include Alacris Theranostics, Editas Medicine, and Veritas Genetics. In addition to Dr. Church, co-founders of GRO Biosciences—and their roles with the company—include:
- Andrew D. Ellington, Ph.D., professor of biochemistry at University of Texas at Austin, who will also serve on the scientific advisory board.
- Daniel J. Mandell, Ph.D., CEO.
- Christopher J. Gregg, Ph.D., CSO.
- P. Benjamin Stranges, Ph.D., principal scientist.
- Marc J. Lajoie, Ph.D., and Ross Thyer, Ph.D., who will serve the company in advisory roles on a consulting basis.
GRO Biosciences is based at the Harvard Life Lab, a shared laboratory space for high-potential life sciences and biotechnology startups founded by Harvard faculty, alumni, students, and postdoctoral scholars.
