By Daria Khaltourina
Q – Avi, some people, especially people new to biomedicine wonder what science is behind Bioviva’s gene technology which Liz Parrish tested, could you comment on this?
A – Bioviva’s experimental gene therapy is based on solid research. So far, there have been thousands of papers published on telomerase gene therapy, and follistatin gene therapy is currently being tested in clinical trials in humans http://www.nature.com/mt/journal/v23/n1/full/mt2014200a.html. As you know, Dr. Blasco’s research group managed to increase lifespan in mice with telomerase gene therapy http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/.
Q – Is hERT therapy exactly the one as Blasco did on mice?
A – Not exactly. Dr. Blasco’s experiment was conducted in mice and as such Mouse telomerase reverse transcriptase (mTert) was used. While in our case hTERT was used. Additionally, we did not create or perform experiments on hTERT−/− humans
Q – There are a lot of questions from specialists about the details of Bioviva’s therapy. Could you provide the details?
A – Construction of the hTERT vector have been reported in research literature (http://cancerres.aacrjournals.org/content/canres/60/8/2116.full.pdf and http://www.ncbi.nlm.nih.gov/pubmed/10022128). 82 base pairs of hTERT promoter sequences were created.
Q – What exactly AAV was?
A – This is proprietary information
Q – Was AAV integrative or not?
A – No. AAVs do not integrate into the chromosome.
Q – What other interventions were used?
A – immunosuppressant drug Prednisone. This is a standard practice for viral vector based therapy.
Q – Will TERT over expression in T-cells affect the offspring cells?
A – No. Our gene therapy does not affect the germline cells
Q – A lot of people wonder about the mechanism and consequences of this gene therapies. Some scientists propose that gene TERT codes telomerase itself. Gene TERC codes matrix RNA, which builds up telomeres. Isn’t TERT-therapy useless without telomere RNA matrix?
The human telomerase enzyme complex consists of two molecules each of human telomerase reverse transcriptase (TERT), telomerase RNA (TR or TERC), and dyskerin (DKC1). The genes of telomerase subunits, which include TERT, TERC, DKC1 and TEP1, are located on different chromosomes. The human TERT gene (hTERT) is translated into a protein of 1132 amino acids. TERT polypeptide folds with (and carries) TERC, a non-coding RNA (451 nucleotides long). TERT has a ‘mitten’ structure that allows it to wrap around the chromosome to add single-stranded telomere repeats. TERT is a reverse transcriptase, which is a class of enzyme that creates single-stranded DNA using single-stranded RNA as a template. TERT is generally often used in gene therapy to improve telomere length in all animal experiments (http://www.ncbi.nlm.nih.gov/pubmed/25519492).
Q – There are other functions of TERT expression (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460319/ and http://www.ncbi.nlm.nih.gov/pubmed/26786236), but the cells that were checked do not have much of TERT expression. Can you comment of this?
A – Yes, there may be other function of hTERT expression. Measuring the patient’s telomere length in peripheral whole blood cells is an industry standard practice. We want to compare our average telomere length with that of the population and therefore prefer to use clinical testing service providers to test industry standard measurement methods and cells.
Q – What about TERT expression in thymus?
A – The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells or T lymphocytes mature. As such, we have measured the telomere length in white blood cells, which include T cells. Measuring gene expression and telomere length in living adult human is complicated and could pose health risks, due to thymic involution and fine needle biopsy, respectively.
Q – Can you shed more light on the results of the therapy? Which percentage of the cell got transformed?
A – We don’t know that yet. We will be conducting tests to on her before and after skin and blood samples to ascertain this data.
Q – What about other types of cell?
A – We are using lymphocyte testing at this time, as it is the most advanced and well understood way to test telomere length today. We are going to measure telomere length and telomerase expression in other tissues in the near future.
Q – What clinical meaning would increase in leukocyte telomere have?
A – Short telomeres in humans have been associated with many chronic diseases of aging http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318193/. We are using lymphocyte testing at this time, as it is the most advanced and well understood way to test telomere length today. We hope to show the same in other tissues. Improved telomere length should mitigate the risk of chronic disease of aging.
Q – Does Bioviva plan to publish research paper in a scientific journal?
A – BioViva is a engineering and implementation company, and not an R&D facility. We rely on replicable and reliable work being done in research labs all over the world. We then translate this work for human use as soon as possible. Members of our scientific advisory board each have published hundreds of peer-reviewed papers. Additionally, Dr. Bill Andrews, a member of our scientific advisory board, is one of the discoverers of the telomerase gene and specifically publishes peer-reviewed papers on that topic. Researches file papers, companies file patents, and we have done that. Finally, we will be publishing our clinical data on website soon as we have it.
Q – Was the question about other ways to senescence missed, explained earlier or delayed?
Here is a thorough explanation about Telomere, Telomerase and Senescence. This detailed essay has over 50 citations. This has been written by our colleague and research biogerontologist Dr. João Pedro de Magalhães and his team. Source: http://senescence.info/telomeres_telomerase.html
See Liz’s Telomere report by Spectracell Laboratories: