Topical application of heterologous protein-expressing Staphylococcus epidermidis for potential therapeutic treatment of skin diseases

PROJECT SUMMARY
Current treatment options for a number of skin diseases generally aim for symptomatic relief and
fail to address underlying pathophysiological changes leading to skin disease In the case of
genetic mutations that cause loss of function mutations supplementation of the missing protein
is a viable approach to treatment However delivery of functional protein to the target
keratinocytes presents a significant challenge moreover the cost of protein production and
purification creates a significant hurdle to developing a commercially viable treatment Finally
given the natural turnover rate in the skin constant reapplication of protein would be needed
which compounds issues related to cost of treatment adherence and convenience
Azitra is a preclinical company focused on microbiome based therapeutics We are developing a
platform that consists of an engineered S epidermidis that is able to establish residence on
human skin and secrete therapeutic protein in situ An ointment with an inoculum of such bacteria
could be infrequently applied to skin providing constant low cost convenient delivery of
therapeutic protein Natural properties of S epidermidis also include secretion of antimicrobial
peptides against S aureus and stimulation of regulatory T cells making S epidermidis an ideal
secretion platform
The proposed Phase I research plan will focus on proof of concept studies to determine the
spatio temporal growth characteristics of our S epidermidis production and delivery system Aim
and to characterize the spatio temporal dynamics of sGFP that secreted by S epidermidis in
a skin equivalent model Aim In the next phase Phase II following this STTR Phase I project
The application of this platform will be tested with filaggrin secreted by S epidermidis in pre
clinical models of atopic dermatitis PROJECT NARRATIVE
The proposal aims to establish proof of concept that a platform can be developed that consists of an
engineered commensal skin bacterial species that is able to establish residence on a skin model and secretes
a desired protein that can penetrate the stratum corneum The small business partner Azitra Inc is currently
developing preclinical candidates using bacterial systems for in situ protein delivery for treating skin diseases
The academic partner Yale University has world class facilities and subject matter expertise to co direct
experimentation and key analyses Together we are aiming to test if this platform is a viable approach as a
therapeutic for treating a range of skin diseases by simultaneously modulating the skin microbiome and
secreting proteins in situ for therapeutic benefit