Benitec lassoos new 'minicircle' plasmid technology

Queensland gene-therapy company Benitec Ltd (ASX:BLT) has licensed-in a novel, non-viral new technology from Stanford University that delivers prolonged RNAi-induced gene-silencing in mammalian cells.

Benitec has signed an licensing arrangement that gives it exlusive rights to exploit the 'minicircle DNA' technology developed by Mark Kay, professor of paediatrics and genetics at Stanford. Kay is now a scientific consultant to Benitec since the Australan company acquired Californian RNAi therapeutics company Avocel early this year.

Kay's 'minicircle' is a custom-designed plasmid -- a loop of DNA of the type that bacteria employ to duplicate exchange genes that confer survival advantages, such as antibiotic-resistance genes.

Gene therapy researchers have been experimenting with delivering new genes and RNAi gene-silencing constructs, using adenoviruses that harmlessly infect mammalian cells, and transiently express their plasmid-coded transgenes. Unlike retroviruses, adenoviruses do not integrate their plasmids permanently into the host cell's genome, so expression of their on-board transgenes is usually temporary -- sometimes, too short-lived to achieve the desired therapeutic benefit.

Kay's minicircle plasmids are plug-and-play genetic 'cassettes' designed to accommodate and express transgenes. By removing all trace of bacterial DNA sequences, and using only human DNA, his team has been able to prolong expression by as much as 500 times over conventional, bacterial plasmids, with no sign of toxicity or adverse side-effects.

His Stanford team has demonstrated stable transgene expression, and significant down-regulation of target genes in mice, lasting up to 10 months. Prolonged transgene expression is essential for effective silencingof cancer-causing oncogenes in tumours, or to eliminating viral infections like hepatitis C and HIV, applications for which Benitec is developing its RNAi therapeutics.

Under its agreement with Stanford, Benitec retains the power to sub-license rights for all applications of RNAi therapeutics -- a provision that would allow Benitec's potential commercial partners or collaborating research agenies to exploit the technology.

Benitec's CEO and executive chairman, Dr John McKinley, said the licence would enhance the company's ability to build effective RNAi therapeutics for its in-house disease programs, and support its broad, pathfinder approach to developing RNAi therapeutics.

Look out for the October-November issue of Australian Life Scientist magazine, which will feature a major examination of RNAi technology.