Rexin-G, a targeted genetic medicine for cancer.
BACKGROUND
Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US.


METHODS
This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US.


RESULTS
In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product.


CONCLUSIONS
Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.
Gordon
Erlinda M
EM
Epeius Biotechnologies Corporation, 475 Huntington Drive, San Marino, CA 91108, USA. egordon@epeiusbiotech.com
Hall
Frederick L
FL
D000818:Animals; D056766:Cyclin G1 / Q000235:genetics*; D019317:Evidence-Based Medicine; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000090063:Proto-Oncogene Mas; D016896:Treatment Outcome
C534702:CCNG1 protein, human; D056766:Cyclin G1; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas