Research and Development
Overview
Osel is the leading company in the emerging field of Bacterial Therapeutics and a pioneer in the development of genetically modified vaginal Lactobacillus.Business approach is based on recent scientific discoveries demonstrating the vital role of naturally occurring beneficial bacteria in the maintenance of health and the prevention of disease. Mission is to harness the protective properties of these specialized non-pathogenic bacteria. This strategy has served as the basis for a series of innovative products initially targeted at prevention and treatment of diseases of the genitourinary and gastrointestinal tracts.
The mucous membranes of humans and animals are densely populated with commensal bacteria, which play an important role in host defense against pathogenic organisms. In the vaginal mucosa, for example, a deficiency of hydrogen peroxide-producing lactobacilli has been associated with an increased risk of bacterial vaginosis, urinary tract infections, and sexually transmitted infections, including Human Immunodeficiency Virus (HIV-I) and Herpes Simplex Virus-2 (HSV-2). A deficiency of vaginal lactobacilli has also been linked to adverse pregnancy outcomes. Similarly, disruption of the protective gastrointestinal microflora can lead to diarrhea, intestinal infections and colitis, as exemplified by antibiotic-associated diarrhea and Clostridium difficile disease.
Osel’s technologies are focused on harnessing the mucosal microflora in two complementary ways. First, we identify the most appropriate naturally occurring bacteria to treat and prevent diseases caused by disruptions in the protective microflora. Second, we develop technologies to genetically enhance the capabilities of these bacteria to combat disease-causing organisms, represented by the MucoCept line of second-generation products.
MucoCept Technology
Osel is pursuing an innovative strategy to prevent the transmission of viral diseases in humans. This strategy is effected by our platform technology, known as MucoCept. The MucoCept approach involves the use of proprietary technology designed to harness the natural microbial flora and its associated biofilm on mucosal surfaces – the site of entry of most viruses – to neutralize viral particles before infection of the host cell can occur. This approach may be used to prevent infection by a number of viruses in humans, including HIV-I and HSV-2. Dr. Peter P. Lee is the inventor of the MucoCept concept and a co-founder of Osel, Inc.
MucoCept
The cervico-vaginal mucosa serves as the major portal of entry for sexually transmitted pathogens in women worldwide. Female-initiated preventative measures are urgently needed to help curtail the HIV/AIDS pandemic worldwide.
In healthy women of childbearing age worldwide, the Lactobacillus species most commonly isolated from the reproductive tract include L. crispatus, L. jensenii, L. gasseri, and L. iners. They are phylogenetically different from food and/or environmental Lactobacillus species.
Non-pathogenic commensal bacteria may be exploited to help prevent transmission of mucosally transmitted viruses at these sites. In this approach (U.S. Patent #5,733,540), vulnerable mucosal surfaces will be colonized with commensal bacteria genetically modified to produce high levels of potent HIV-binding proteins as either secreted or surface-displayed molecules to sequester viruses, thus impeding the access of viruses to underlying epithelial cells and lymphocyte targets. These trapped viruses can sequentially be inactivated locally by antiviral compounds, such as lactic acid and hydrogen peroxide, secreted by the lactobacilli. The inactivation could abort the infection process and/or significantly reduce the number of infectious viral particles.
This novel approach will create a barrier to HIV transmission that is different from, yet compatible with, current antiviral therapies, future vaccines and other barrier methods. It will also be inexpensive to manufacture, store, and distribute. As a live, self-renewing microbicide, it does not have to be administered at the time of sexual activity, i.e. it is coital-independent. Administration is discreet and fully controlled by the female users. Since the Lactobacillus strain used is a commensal organism normally present in the human vagina and associated with vaginal health, its potential toxicity is expected to be low or nonexistent compared to chemical agents, which often harm both the normal protective bacterial flora and the underlying mucosal epithelial cells. This approach has potential utility against pathogens other than HIV.
Over the past several years, Osel has made substantial progress in the development of this novel topical microbicide, with a key proof-of-concept study published in the Proceedings of the National Academy of Sciences [PNAS, 2003, 100:11672-11677]. The genome of several human vaginal Lactobacillus isolates has been sequenced in collaboration with Broad Institute of MIT and Harvard. We have identified native regulatory elements and sites for chromosomal integration of heterologous genes. L. jensenii 1153 has been engineered to efficiently express highly potent anti-HIV proteins (Antimicrob Agents Chemother 2006, 50, 3250-3259; Applied and Environmental Microbiology 2008. 74, 4626-4635). Currently, a preferred MucoCept product candidate has been evaluated in a non-human primate of vaginal Lactobacillus colonization (J. Med. Primatology 2008, in press), and is being optimized for manufacturing and formulation. The development of this MucoCept bacterium represents a major step towards the advancement of an inexpensive, yet durable, protein-based microbicide to address the urgent need for female-initiated approaches to block the heterosexual transmission of HIV.
The MucoCept program is supported in part by NIH/NIAID IPCP, Partnerships for Topical Microbicides, Microbicide Innovation Program, CONRAD Global Microbicide Project, and the International Partnership for Microbicides.