Technology
SASPjectTM - A lethal injection for bacteria
Phico Therapeutics is developing a novel platform technology for
anti-bacterials which will side-step current resistance mechanisms
and result in products which potentially have fewer side effects
than conventional antibiotics. The technology, known as SASPjectTM,
is an entirely novel concept in antibacterial therapy, combining
a very broad spectrum antibacterial protein (SASP) with a delivery
vector that can be programmed to target selected bacteria. Phico's
technology meets the criteria for the ideal antimicrobial agent
and offers additional unique benefits:
- SASPjectTM has a completely novel mode of action.
- SASPjectTM technology can be used against all bacteria, including
those which are multiply antibiotic resistant, with the advantage
that it can be targeted to individual or multiple bacterial species.
- The opportunity for resistance to SASPjectTM to develop is severely
limited with the active ingredient, SASP, targeting and inactivating
a fundamental and crucial bacterial cell component - DNA.
- SASPjectTM ensures the permanent loss of bacterial viability is
not accompanied by immediate bacterial cell lysis (i.e. bursting
of bacterial cells releasing toxins and other inflammatory cell
components).
- SASPjectTM can inactivate antibiotic resistance genes - a feature
which is not available from any conventional antibiotic.
In the presence of SASP bacteria cannot replicate, protein production
is halted preventing an increase in the levels of toxins and antibiotic
resistance determinants and, most importantly, targeted bacteria
cannot survive.
SASPjectTM comprises two components, firstly a unique antibacterial
protein, known as SASP, and secondly, a vector that will deliver
and inject the gene encoding SASP into targeted bacteria. Once produced
inside bacteria SASP binds to and inactivates a universal and essential
bacterial cell component - its DNA. Functional DNA is crucial to
cell survival so once this cellular component is inactivated the
bacterial cell cannot metabolise or reproduce. SASP has the effect
of 'turning off' the DNA and under these conditions cellular functions,
including gene expression, become inhibited. This means that the
bacteria stop producing toxins and stop dividing, halting the spread
of infection and allowing the immune system time to remove the bacteria
from the body.
Although the gross effect of SASP is to inactivate chosen bacteria,
its use has important additional benefits, since SASP can bind to
and inactivate all the DNA inside bacteria, including plasmid DNA
which is a common source of antibiotic resistance genes. SASP can
therefore actively help to prevent the spread of antibiotic resistance
and toxin genes.
A feature of significant importance is that SASP binds to all bacterial
DNA, irrespective of the sequence of that DNA. Spontaneous mutations
in DNA, or the import of new DNA, giving new characteristics to
the bacterial cell are key ways in which bacteria develop resistance
to antibiotics - neither of these strategies will affect the ability
of SASP to bind to and inactivate bacterial DNA.
The role of Phico's delivery vector is simply to target selected
bacteria and to inject the SASP gene into those bacteria. For this
purpose, Phico utilises fully characterised bacterial viruses (bacteriophages)
as the starting point and modifies and simplifies these so that
they retain only the required characteristics. Bacteriophages, and
Phico's delivery vector, can target only bacterial cells and no
other cell type. Thus, the delivery vector acts as a syringe, injecting
the SASP gene into bacterial cells where SASP causes inhibition
of bacterial cell function with concomitant irreversible loss of
viability.
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In essence, Phico's technology can be considered a 'lethal injection for bacteria'.