ADViSYS Inc.
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Viral Genomix Inc. was founded in April of 2000 ; In 2006, it changed its name to , VGX Pharmaceuticals Inc. . This is the "root" of the corporation that eventually becomes known as Inovio Pharmaceuticals, Incorporated.
[...]
In 2005, Genetronics Biomedical Corporation purchased a Norwegian company called Inovio AS ( Source: [HW009F][GDrive] ); shortly afterwards, this combined corporation was renamed to Inovio Biomedical Corporation .
- NOTE: The technology from Inovio AS became part of VGX Pharmaceuticals Inc. , when in 2009, VGX Pharmaceuticals Inc. purchased Inovio Biomedical Corporation.
In Feb 2007, VGX Pharmaceuticals Inc. purchases/merges with ADViSYS Inc. .
In June 2009, VGX Pharmaceuticals Inc. purchased Inovio Biomedical Corporation , and the combined company was retained the name Inovio Biomedical Corporation . In May 2010, Inovio Biomedical Corporation was renamed to Inovio Pharmaceuticals, Incorporated.
[...]
Also see
OVERVIEW/SUMMARY ARTICLES
2001 book - "Everybody Wins! A life in free enterprise" by Gordon Cain, pages 261-262
PDF (with OCR) of pages 261 an 262 : [HB007W][GDrive]
- Publisher : Chemical Heritage Foundation, 2001 - Chemical engineers - 353 pages
- Book Summary : Everybody Wins! is the inspiring, unfamiliar picture of an individual launching a wholly new career not once, but twice when most are ready to retire. In his 70s Gordon Cain, a chemical engineer by trade, acquired and restructured several chemical companies, effecting a turnaround in the commodity chemicals industry. An unprecedented visionary, Cain made millions for himself and his employees through the strategies of innovative management, employee stock ownership, and leveraged buyouts. In his 80s he turned his interests to a new economy field—biotechnology. Within only six years he transformed one company, Lexicon Genetics, from a university-based start-up to a public company worth over one billion dollars, while masterminding two more biotech companies. The second edition talks about these recent ventures. As Cain recounts with modesty and humor how he made his way from chemical engineer to millionaire-entrepreneur, we are reminded of how America's free-market economy provides unparalleled opportunity and how good business deals can benefit everyone. In the process this book illustrates how entrepreneurs continually reinvent themselves.
Applied Veterinary Systems, Inc.
In 1997 the Baylor College of Medicine Development Company brought us yet another new technology, this one aimed at stimulating the pituitary gland in pigs to make them grow faster and leaner. This new technology was the outgrowth of research by Robert Schwartz, Bert O'Malley, and Ruxandra Draghia at Baylor. Bill McMinn and I [, Gordon Cain, ] decided to fund additional research on this project, and in November 1997 we established a company called Applied Veterinary Systems, Inc. (AVS), with initial funding of $250,000 for this research.
We quickly discovered that the injection of small amounts of a growth hormone-releasing hormone (GHRH), or of expression vectors of GHRH, enhanced the secretion of the natural growth hormone from the pig's pituitary gland. Further improvements to this injection process resulted from applying electroproration (rapid electroshock) to the muscle at the injection point. The injection and electric stimulation have enhanced growth rate and improved the meat-to-fat ratio in the pigs. Additional research shows possible use for GHRH in beef and dairy cattle as well as in companion animals.
Today research is centered on reducing the costs of the fermentation process used to produce GHRH or expression vectors thereof and exploring the parameters of electroproration, which include duration of pulses, voltage, and amounts of injected material, to determine maximal condition. In addition, we have found that the injection of GHRH into pregnant sows results in a pass-through of the hormone to the piglets born in the litter, with favorable results.
Hog inventories in 1999 in the United States were 62.2 million head, and pork production reached a record 8. 7 million tons. In China, the world's largest pork producer, hog inventories were 396 million head in 1999.
Other countries with large pork production include Canada, Brazil, and the European Union. Pork represents almost 39 percent of world meat production. This obviously represents an enormous market for any product that can significantly reduce pork production costs and favorably influence the meat-to-fat ratio. Initial contacts have been made with the FDA as to the protocol needed for securing their approval for using our product in food animals in general and in pigs in particular. FDA approval is required for use in the U.S. markets.
Most of our research to date has been concentrated on the hog market, where our test results show enormous potential. However, some early work suggests that this same technology can be applied to companion animals-cats and dogs-leading to longer life spans. The market potential here is significant with the American Veterinary Medical Association, estimating the total companion dog population to be 52 .8 million and the total companion cat population to be 59.6 million. While FDA approval would be required to serve this companion animal market also, the approval process would likely take only one half the time required for food animals.
Today we are actively pursuing market strategies and FDA approval and continuing tests on larger and larger groups of animals.
EVIDENCE TIMELINE
1997 (Nov) - New company called Applied Veterinary Systems, Inc. (AVS) is created with initial funding of $250,000 for this research; Spun out of the Baylor College of Medicine Development Company (Texas)
Source : 2001 book "Everybody Wins! A life in free enterprise" by Gordon Cain, pages 261-262 ( see [HB007W][GDrive] )
"In 1997 the Baylor College of Medicine Development Company brought us yet another new technology, this one aimed at stimulating the pituitary gland in pigs to make them grow faster and leaner. This new technology was the outgrowth of research by Robert Schwartz, Bert O'Malley, and Ruxandra Draghia at Baylor. Bill McMinn and I [, Gordon Cain, ] decided to fund additional research on this project, and in November 1997 we established a company called Applied Veterinary Systems, Inc. (AVS), with initial funding of $250,000 for this research."
Early description of ADViSYS available on the archived 2003 www. advisys.net website ( https://web.archive.org/web/20030624023705/http://www.advisys.net/ )
"ADViSYS was formed in 1997 to develop animal applications for a new growth hormone releasing hormone (GHRH) treatment system. With technology licensed from Baylor College of Medicine, ADViSYS has established that using this GHRH technology improves health, welfare, and quality of life in animals. Results from several large-scale tests in different species have shown that a single dose of GHRH can cause animals to produce optimal levels of their own natural growth hormone thus significantly improving health and welfare in companion and production animals. ADViSYS technology also has the potential to increase the quality of life of cancer-afflicted dogs undergoing chemotherapy and/or radiation treatments."
Locaiton of early offices (Baylor College of Medicine, Zip code ... )
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Company : ADViSYS, Inc.
Filing Date : 1999-03-11
Filing Number : 00000003443825
Filing Type : Application For Certificate Of Authority
Filing Code : 000000000235
Company Number : 0012566706
Status : Forfeited Existence
Incorporation Date : 11 March 1999 (about 24 years ago)
Dissolution Date : 24 July 2009
Company Type : Foreign For-Profit Corporation
Jurisdiction : Texas (US)
Branch : Branch of Delaware (US) company
Registered Address : 2700 RESEARCH FOREST DRIVE SUITE 180 / THE WOODLANDS / 77381 / TX, USA
Alternative Names : APPLIED VETERINARY SYSTEMS, INC. (trading name, 1999-03-11 - 2001-09-17)
directors [ As of the dissolution of the company ]
DOUGLAS R KERN, director
DOUGLAS R KERN, president
Douglas R Kern, agent
HENRY L HEBEL, vice president
MARY ALICE BERGAN, director
MICHAEL CHAMBERS, director [ <-- also with ALDEVRON ? ]
RONALD BERGAN, director
2001 (Sep 18) - Change of name to ADViSYS, Inc.
Source : Open Corporates page for "ADViSYS" (Saved as a PDF : [HW00AH][GDrive] ). It says that the name was still officially "APPLIED VETERINARY SYSTEMS, INC. (trading name, 1999-03-11 - 2001-09-17)". This suggests that starting September 18 2001, the name of the OpenCorporates entry "ADViSYS" was used.
2001 - Move of office to The Woodlands, Texas ...
Source : 2019 (December 06) - Legal filing, VGXI, INC. (Plaintiff) vs ALDEVRON LLC, (Defendant) ( See Saved PDF : [HX0039][GDrive] ) ; Full text also on page for Aldevron
"A predecessor to VGXI, ADViSYS, was founded in 1997 as a gene therapy company to develop technology for optimized, large scale plasmid DNA production and purification. [...] In 2001, ADViSYS opened their offices in The Woodlands, Texas as a spin-off from Baylor College of Medicine. VGXI’s headquarters remains there today."
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2002 (Feb 1) - EMPLOYMENT AGREEMENT for Ruxandra Draghia-Akli
THIS EMPLOYMENT AGREEMENT (the "Agreement") is made effective the 14th day of November, 2001 between ADViSYS, Inc. ("ADViSYS"), a Delaware corporation, with its place of business at 2700 Research Forest Drive, Suite 180, The Woodlands, Texas, 77381and Ruxandra Draghia-Akli ("Employee") whose residence address is 5215 Starkridge Drive, Houston, Texas, 77035.
https://www.sec.gov/Archives/edgar/data/1055726/000104746909000344/a2190045zex-10_28.htm
Starting February 1, 2002 ... During the employment period, Employee shall serve as Research Team Leader of ADViSYS under the President of ADViSYS, with such duties and responsibilities that are customarily assigned to such position and such other duties and responsibilities as may be from time to time assigned to him by the President of ADViSYS.
https://vitalrecord.tamhsc.edu/hsc-ibt-director-assists-in-first-ever-approved-dna-therapy-for-food-animals/
2003 (Jan 02) - FASEB Journal express article : "High-efficiency growth hormone releasing hormone plasmid vector administration into skeletal muscle mediated by electroporation in pigs"
Received July 29, 2002; accepted November 25, 2002
https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.02-0671fje
https://sci-hub.ru/https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.02-0671fje
draghia-akli2003.pdf
The FASEB Journal express article 10.1096/fj.02-0671fje. Published online January 2, 2003.
Ruxandra Draghia-Akli,*,. Kenneth M. Ellis,. Leigh-Anne Hill,*,. P. Brandon Malone,*,. and Marta L. Fiorotto.
*Department of Molecular and Cellular Biology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030; .Applied Veterinary Systems, Inc., Houston, Texas 77030; .USDA-ARS Children Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030 Corresponding author: Ruxandra Draghia-Akli, Research Team Leader, Advisys, Inc., 2700 Research Forest Drive, Suite 180, The Woodlands, TX 77381. E-mail: ruxandradraghia@advisys.net
ABSTRACT
We report here a very efficient method for the in vivo transfer of therapeutic plasmid DNA into porcine muscle fibers by using electric pulses of low field intensity. We evaluated delivery of 0.1.3 mg of plasmid vectors that encode reporter secreted-embryonic alkaline phosphatase (SEAP) or therapeutic growth hormone releasing hormone (GHRH). Reporter gene studies showed that internal needle electrodes give a 25-fold increase in expression levels compared with caliper electrodes in skeletal muscle in swine. Dose and time courses were performed. Pigs injected with 0.1 mg plasmid had significantly greater weight gain than controls over 53 days (22.4 ± 0.8 kg vs. 19.7 ± 0.03 kg, respectively; P<0.01). The group treated with GHRHexpressing plasmid at 14 days of age demonstrated greater weight gain than controls at every time point (25.8 ± 1.5 kg vs. 19.7 ± 0.03 kg; P<0.01). Body composition studies by dual X-ray absorbitometry showed a 22% decrease in fat deposition (P<0.05) and a 10% increase in bone mineral density (P<0.004). Our studies demonstrate that by optimizing the electroporation method, favorable physiological changes, such as enhanced weight gain and improved body
composition, can be obtained at extremely low plasmid doses in a large mammal.\
MATERIAL AND METHODS
DNA constructs
Plasmid vectors containing the muscle-specific synthetic promoter SPc5.12 were described previously (31). Mutated porcine GHRH cDNAs were generated by site-directed mutagenesis of GHRH cDNA (Altered Sites II in vitro Mutagenesis System, Promega, Madison, WI), and cloned into the BamHI/HindIII sites of pSPc5.12 to generate pSP-GHRH. The 3’ untranslated region of growth hormone was cloned downstream of GHRH cDNA (14). The pSP-secreted embryonic alkaline phosphatase (SEAP) construct contains the SacI/HindIII SPc5.12 fragment, SEAP gene, and SV40 3’UTR from pSEAP-2 Basic Vector (Clontech Laboratories, Palo Alto, CA).
Electroporation devices
A BTX T820 generator (BTX, division of [Genetronics Biomedical Corporation], San Diego, CA) was used to deliver square wave pulses in all experiments. We used voltage conditions of 100.200 V/cm, six pulses, 60 ms per pulse. Caliper and needle electrodes (BTX) were used to deliver in vivo electric pulses. The caliper electrodes consisted of 1.5-cm square metallic blocks mounted on a ruler, so that the distance between the plates could be easily assessed; the six-needle device consisted of a circular array (1 cm diameter) of six equally spaced filled, 21-gauge needles mounted on a nonconductive material. All needles were 2 cm in length. In all injections, the needles were completely inserted into the muscle.
ACKNOWLEDGMENTS
We thank Dr. Robert J. Schwartz for useful discussions and support; Dr. Doug Kern and
Advisys, Inc., for support and invaluable expertise; and Dr. Louis C. Smith for critical correction
of the manuscript. We would especially like to thank Ms. Catherine Tone for attentive revision
and editing the manuscript. We also thank Jim Cunningham, Frankie Biggs, Craig Stubblefield,
and Michael Stubblefield for excellent care of the animals; Dr. Harry Mersmann and Roman
Shipaylo for the body composition data; and Genetronics Inc., for providing us the injectable
electrodes. This project has been partially funded by the U.S. Department of Agriculture,
Agricultural Research Service, under cooperative agreement no. 58.6250.6001. The contents of
this publication do not necessarily reflect the views or policies of the U.S. Department of
Agriculture nor does mention of trade names, commercial products, or organization imply
endorsements by the U.S. Government.
References - Used JA Wolff paper...
2. Danko, I., and Wolff, J. A. (1994) Direct gene transfer into muscle. Vaccine 12, 1499.
1502
2004
https://web.archive.org/web/20040731015520/http://www.advisys.net/
Our Company
ADViSYS was formed in 1997 as a Baylor College of Medicine Technology start-up company to develop and commercialize animal applications of growth hormone releasing hormone technology. Since 1997, ADViSYS has successfully developed and tested this unique technology that improves the health and quality of life in animals. In several large scale trials, these proprietary injectable plasmid-based products have been shown to significantly improve the health status and immunity of pigs and cattle with only a single dose. This new technology has also shown the potential to increase life expectancy, decrease anemia, and improve the quality of life of cancer-afflicted dogs undergoing radiation treatment and chemotherapy.
ADViSYS intends to use this plasmid-based system to deliver other small proteins for disease prevention and therapeutic use. To achieve this goal we have developed cutting-edge technologies for the design, production, and delivery of plasmid-based DNA constructs. Based on our expertise in product development, manufacturing, and regulatory strategy, ADViSYS intends to expand its business to assist other companies in the development of their biopharmaceuticals and delivery systems as well as other medicinal products.
Our Technology
ADViSYS has developed a new biopotential enhancement technology platform that allows the company to leverage applications discovered out of one species across multiple markets. The ADViSYS system is the result of leading-edge technology on multiple fronts:
Proprietary Plasmid Expression Vector: Some of our plasmid systems contain muscle-specific elements that drive the expression of GHRH, while others encode for different intracellular or secreted proteins and are under the control of ubiquitous or tissue-specific promoters. Our library of novel GHRH analogs and promoters provides a rich product pipeline, and has given the ADViSYS team a broad range of experience in optimizing expression of secreted proteins.
Electrokinetic Delivery System: ADViSYS has developed proprietary technology for delivery of plasmids into skeletal muscle cells. This unique technology optimizes plasmid uptake and subsequent expression. When plasmids with historically low expression levels are delivered with our electrokinetic device, clinically effective results have been achieved.
Plasmid Production Process: ADViSYS has developed a proprietary plasmid manufacturing scheme with process advantages that make it cost effective and scaleable. Our process does not use any animal-derived products, carcinogens, organics or flammables and is therefore safe and acceptable to all regulatory agencies.
©2004 ADViSYS, Inc. All Rights Reserved
Please send questions or comments to info@advisys.net
2003 - ADViSYS Electroporation Enducer (designed by Paragon Innovations) - With a new technology : "Pulsed constant-current control"
https://cdn.thomasnet.com/ccp/30208803/276586.PDF
2005-paragon-innovations-summary-advisys-electroporation-enducer-276586.pdf
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(also see - https://www.paragoninnovations.com/case-studies/advisys.htm )
2005 (May)
https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(05)00430-2
NAKED DNA GENE TRANSFER: CHROMOSOMAL, INTEGRATION, DELIVERY TECHNIQUES| VOLUME 11, SUPPLEMENT 1, S74-S75, MAY 2005
190. Improvement of Electroporation Devices and Methods for Use with Plasmid-Based Therapeutics and DNA Vaccine Applications in Small and Large Animals
190. Improvement of Electroporation Devices and Methods for Use with Plasmid-Based Therapeutics and DNA Vaccine Applications in Small and Large Animals
Open ArchiveDOI:https://doi.org/10.1016/j.ymthe.2005.06.193
Amir S. Khan,1 Ruxandra Draghia-Akli,1
1 Research, ADViSYS, Inc., The Woodlands, TX.
Introduction. Most commercially available electroporation (EP) technologies are based on constant-voltage concepts. Due to variations in tissue resistance during the EP process, a predetermined voltage pulse may cause an unregulated increase in the current flowing through the tissue during the duration of the pulse and result in loss of the perfect square-wave function, tissue damage, pain and reduced plasmid uptake and expression. The unregulated current generated with conventional electroporation devices may generate amounts of heat in tissues that can easily kill cells. To dramatically improve plasmid uptake and expression levels, we have developed an electrokinetic device (EKD) as well as a single-use electrode array.
EP Components. The ADViSYS EP technology system is software driven, includes the battery-powered EKD enclosed in a water-proof case, an EP handle and five-electrode array for large animals (dogs, pigs, cows, horses, etc.) as well as a three-electrode array designed for small animals (rodents). The ADViSYS EKD is portable and is specifically designed to be used in both laboratory and field conditions.
Constant current data. During the course of the EP, the EKD unit records the current and voltage and stores the data, which can then be downloaded and stored electronically to verify optimal EKD function. The EP parameters are monitored by the EKD during each pulse. When the resistance changes during the EP, the voltage will be adjusted such that the current is kept constant throughout each pulse. Typically, for current intensities of 0.4 to 0.6 Amps, and in response to varying tissue resistance during the electroporation procedure, the voltage varies between 80 and 130 V/cm to maintain a constant current. Nevertheless, the voltage necessary to ensure a certain current intensity varies with the species, age and size of the animal, and it is influenced by muscle and fiber size, fat and interstitial fiber content of tissues, collagen, water content, etc. For instance, the pulse characteristics were recorded and analyzed in young pigs (approximately 11 kg), 3 to 4 weeks of age. In this case, for a current intensity of 0.6 Amps, the voltage varies between 110 and 130V for the three pulses, parallel to the tissue resistance of 170 to 230 Ohms. We also measured the pulse characteristics for the same current intensity of 0.6 Amps, in one-year old pigs, weighing 177 kg. In this case, the voltage varied between 80 and 120V, with a tissue resistance of 145 to 190 Ohms. Thus, it is apparent that simply trying to maintain a constant voltage does not result in ideal electroporation conditions for each individual animal and should be optimized for each different species and application. We have also shown that tissue damage results in decreased transgene expression for therapeutic and vaccination applications and results from mice cannot be easily extrapolated to larger mammals.
Conclusions. The constant-current EKD that was designed and built by ADViSYS maintains a square-wave function in the target tissue irrespective of changes in tissue resistance. This versatile technology can be applied to facilitate plasmid delivery in both large and small animals.
Article info
Identification
2006 (May)
https://pubmed.ncbi.nlm.nih.gov/16150516/
Vaccine
. 2006 May 22;24(21):4607-14. doi: 10.1016/j.vaccine.2005.08.049. Epub 2005 Aug 24.
Successful parallel development and integration of a plasmid-based biologic, container/closure system and electrokinetic delivery device
Henry Hebel 1, Heather Attra, Amir Khan, Ruxandra Draghia-Akli
Affiliation
1
ADViSYS Inc., 2700 Research Forest Drive, Suite 180, The Woodlands, TX 77381, USA. henryhebel@advisys.net
PMID: 16150516
Abstract
We have developed three major technologies that allow plasmid-based products to be used for large-scale vaccination or therapeutic protein applications. Our team has integrated these components into one complete, cost-effective, easy-to-use system capable of rapid implementation under field conditions. The proprietary manufacturing process uses a lysis method and membrane-based chromatography to rapidly produce large-scale batches of plasmid. Plasmid doses are filled into the Becton-Dickinson Uniject container/closure system. The Uniject adapts to the electrode array of our constant current electrokinetic device, such that the plasmid is delivered in the area of tissue defined by the electrodes. Thus, plasmid uptake and expression levels are dramatically improved. This is the first completely integrated delivery system for plasmid-based products.
2006 - "Inovio tested an electroporation device, developed by a Texas company called [ADViSYS Inc.], to immunize monkeys against a form of HIV."
Source : 2016 (Dec 16) - Wall Street Journal : "America’s Next Defense Against Zika and Other Foreign Invaders" ( By Betsy McKay and Peter Loftus / PDF of saved source : [HN022L][GDrive] )
Also see : Zika virus epidemic (2015-2016) /
[...] Inovio, based in Plymouth Meeting, Pa., also began a 10-month trial this summer with 160 participants in Puerto Rico, where Zika spread rapidly.
Dr. Kim, the company’s 47-year-old chief executive, got his Ph.D. in biochemical engineering at the University of Pennsylvania, where he met David Weiner, a biologist and now a director at Inovio.
After working in vaccine manufacturing and research at Merck & Co., Dr. Kim co-founded a company called Viral Genomix in 2000. The company later acquired a San Diego-based company called Inovio and took its name.
Inovio explored experimental DNA vaccines for HIV, among other technologies. At the time, the vaccines showed promise in animal studies, but failed in humans when given via standard vaccine injections.
Drs. Kim and Weiner turned to electroporation—first tried in the 1980s to boost the effectiveness of chemotherapy. In 2006, they tested an electroporation device, developed by a Texas company called [ADViSYS Inc.], to immunize monkeys against a form of HIV.
One evening, close to midnight, Dr. Kim’s home phone rang. It was Dr. Weiner calling to say the HIV vaccine, assisted by the electroporation device, had kick-started an immune response in the monkeys.
“That really triggered the path we’re on now,” Dr. Kim said. His company acquired [ADViSYS Inc.] in 2007. [...]
Ruxandra - ALSO WITH COMPUVAC !!!!!
Also at the GoF symposium ...
https://events.eurordis.org/ecrd2022/speaker/477716/ruxandra-draghia-akli
ruxandra-draghia-akli.pdf
Speaker Details
Full Name
Dr Ruxandra Draghia-Akli
Job Title
Global Head, Global Public Health R&D
Company/Organisation
Johnson & Johnson
Speaking At
Track F, Session 1 Making Europe attractive for therapies development
Speaker Bio
Ruxandra Draghia-Akli, is Global Head, Johnson & Johnson Global Public
Health R&D, where her and her team advance global public health into the next
era of innovation through discovery, development, and technology capabilities. She accelerates GPH’s end-to-end strategy
by collaborating with teams across Johnson & Johnson on assets with application in global public health settings. Under her
leadership, GPH R&D adds value and generates new external innovation opportunities through our J&J Centers for Global
Health Discovery and other external partnerships.
Ruxandra is a cross-sector leader with experience in industry, government, and academia. She led Medical and Scientific
Affairs for vaccines at Merck, and she worked for the European Commission, first as Director and later as Deputy Director
General, overseeing research and innovation programmatic, legislative, and financial initiatives, leading public-private
partnerships, global programs and consortia, and development of novel research financial instruments, while contributing to
the Commission’s strategy for improving public health. Ruxandra has a track record of unlocking innovation in biotechnology
as both a founder and head of research at ADViSYS, Inc. and VGX Pharmaceuticals (now Inovio Pharmaceuticals).
Ruxandra holds a M.D. from Carol Davila University, Romania, and a Ph.D. in human genetics from the Romanian Academy
of Medical Sciences. She undertook doctoral training at University Rene Descartes in Paris, France and a postdoctoral
training at Baylor College of Medicine, Houston, Texas, with a focus on rare diseases, molecular biology, gene therapy and
novel vaccines. Ruxandra has authored and co-authored more than 100 papers and holds over 100 patents.