Minicircle Gene Therapy Against HIV
Minicircle provides robust long-term, reversible expression of in vivo biologics without altering your preexisting genome. Minicircle is safe, ethical, accessible, and reversible gene therapy that can eradicate disease, reverse aging and transform public health.
Project Team
Institutions
Project Status
Funding Opportunity
Background
As of 2018 nearly 40 million people globally were living with HIV, with over 1.7 million new infections that year. There is currently no reliable cure for HIV, and those living with the disease must continually take anti-retroviral therapies to maintain low viral loads. Anti retroviral therapies are expensive, have side effects, and require daily attention to medications. There continues to be a need for therapeutic interventions with fewer side-effects and patient compliance issues.
Project Details
Minicircles are special plasmids that are engineered to tightly bind the scaffold matrix inside the cell and then to produce antibodies that are secreted into the blood stream. A cocktail of these minicircles can target all the HIV strains via accordingly produced antibodies and neutralize them. We have demonstrated minicircle production of bnAbs in human cell culture and human serum and partnered with two of the most experienced HIV gene therapy clinicians in the world. Minicircle HIV vaccine combinations of bnAbs have been shown to completely neutralize 208 strains of HIV at <1ug/mL. One advantage of the innovation is the ability to treat multiple strains of HIV. These are nucleic acids that encode broadly neutralizing antibodies to HIV. They are suitable for administration to individuals and provide long-lasting expression and secretion of the broadly neutralizing antibodies described into an individual’s blood-stream. As HIV is highly polymorphic, the compositions we use may comprise a plurality of nucleic acids encoding different broadly neutralizing antibodies (or a single nucleotide encoding a plurality of different broadly neutralizing antibodies). Such combinations allow for an off-the-shelf treatment for individuals irrespective of the HIV strain that the individual is infected with. Another advantage of the innovation is the long lasting and low-toxicity nature of the treatment. This advantage is due to the antibodies used being encoded by small nucleic acids known as minicircles and/or mini-intronic plasmids. Both of these types of plasmids are small and lack extraneous sequences of bacterial origin. As a result of their small size, the plasmids are less prone to transcriptional silencing by the cells that take up and express the plasmids leading to long-term expression. Additionally, while antibodies tend to have fewer side effects than small molecule treatments, these plasmids have low immunotoxicity owing to the reduction of immunostimulatory bacterial sequences.
Project Timeline
In vitro / mouse studies
Required Funding$250,000
Statusongoing
Duration6 MonthsIn vitro proof of concept and in vivo mouse studies
In vivo monkey studies
Required Funding$750,000
Statusplanned
Duration6 MonthsIn vivo monkey studies
Phase I Clinical Trials
Required Funding$2,999,996
Statusplanned
Duration12 MonthsWe need to scale up our clinical trials process.