Difference between revisions of "Team:BABS UNSW Australia/project/futureapps"

Introduction

Synthetic organelles are a platform technology from which a range of therapeutic applications can stem. Hormone therapy, monoclonal antibody therapy, supplements for monogenic diseases and siRNA therapy are just a few examples of treatments which could develop from synthetic organelles. Below, we discuss two case studies in more detail.

Case Study 1: endosynbiology and organogenesis

The original idea for endosynbiology came from the endosymbiosis between pea aphids and the Buchnera sp. of bacteria. Buchnera inhabit specific cells in the aphid known as ‘bacteriocytes’ with the specific organ known as the ‘bacteriome’ (1). The bacteria synthesise a range of amino acids to supplement the aphid’s diet of sap. It was this simple idea of supplementation with in vivo protein expression that stimulated visions of synthetic human organs with supplementing or additive functions, and led to our current project. After some major bankruptcies in the early 2000s, the field of tissue engineering is beginning to re-emerge with biologic skin products currently available and tubular structures such as tracheas and arteries in development. Companies such as Organogenesis Inc. are leading the market in regenerative medicines and making the idea of transplantable organs grown in the laboratory a reality (2). Synthetic organelles – organelle engineering, if you like – is the perfect companion to emerge with tissue engineering technology. As we develop the ability to engineer hollow and glandular organs, endowing these with supplementary functions such as synergised insulin secretion or contraceptive oestrogen/progesterone secretion could become a huge component of future medicine. And who knows – maybe one day our Sychechocystis organelle will combine with engineered skin grafts to create the first photosynthetic humans! We can dream, right?

Case Study 2: in vivo biologic

The rise of targeted biologic therapies has dominated in the past few years. In the realm of autoimmune, inflammatory and neoplastic diseases, hundreds of new therapies are being developed to tackle disease from a new perspective [3]. The use of monoclonal antibody therapies and more recently, the development of chimeric antigen receptor (CAR) T cell therapies (4), has made a real difference to treatment by specifically targeting, with antibody affinity, molecules of pathogenesis. Examples of this include anti-TNF-alpha antibodies used in rheumatoid arthritis and trastuzamab, which binds to and blocks the HER2 receptor commonly amplified in breast cancer. One of many problems with this system is that regular injections are required to maintain antibodies within the system. Whilst this is perhaps okay for a disease such as breast cancer, which today has an 80% cure rate, chronic diseases such as rheumatoid arthritis, inflammatory bowel diseases and severe allergic diseases will require lifetime treatment, or substitution with other, less effective drugs. Even CAR T cell therapy, an ingenious in vivo system which exploits the strength of the immune system to tackle blood-borne and solid cancers using the chimeric B/T cell receptors maintained on autologous T cells, has its drawbacks – that it relies on multiple injections. A treatment, not a cure. Future work in endosynbiology provides a solution to this problems. Quickly and easily transforming a bacterial chassis (optimised for endosynbiosis) with the antibody sequence could supply a permanent source of therapy, which is essentially curative.

References