Aa
dd-RNAi compound, Benitec??
Does anybody knows about this drug? Today I received newssetller from hepb.org and they have listed this in their drug watch list.
http://benitec.com/gene-silencing.php#hepb
Looks like they were suppose to start pre clinical studies in Feb 2011.
http://benitec.com/gene-silencing.php#hepb
Looks like they were suppose to start pre clinical studies in Feb 2011.
According to the abstract(see below), it seems they are getting on top of toxicity and safe delivery with their new method. They may also be ahead of benitec.
Doesn't Arrowhead Research Corp has a safe delivery platform for RNAi?
Hepatitis B virus (HBV) is hyperendemic to southern Africa,
east and south east Asia where there are approximately 350 million
chronically infected individuals. Chronic carriers have an increased
risk of developing potentially fatal complications of cirrhosis and
hepatocellular carcinoma. Licensed HBV treatments rarely eliminate
the virus from infected individuals, and improvement of HBV therapy
remains a priority. We have previously demonstrated that CMV and
U6 (Pol II/III) expression cassettes that generate artificial antiviral
RNA interference (RNAi) activators can be used to inhibit HBV gene
expression in vivo. Nevertheless, achieving safe and efficient delivery
of these anti-HBV RNAi sequences remains an important objective.
Recombinant adenoviruses (Ads) are amongst the most efficient
hepatotropic gene delivery vehicles, but a drawback of their use is
transient transgene expression and toxicity resulting from induction
of host immune responses. To limit vector immunostimulation, we
have generated RNAi-activating anti-HBV gutless helper-dependent
(HD) Ads. Efficacy against HBV replication was tested in HBV
transgenic mice, which stringently simulate the human condition of
chronic HBV infection. Two days after intravenous administration
of 5×109 recombinant HD Ads to HBV transgenic mice, 80-90%
of hepatocytes were transduced. Markers of HBV replication were
decreased by approximately 95% in animals receiving the HD Ads
and this effect was sustained for 8 weeks without adverse effects.
Compared to unmodified first generation anti-HBV Ads, inhibition
of viral replication was significantly more sustained. Moreover,
acute hepatotoxicity and proinflammatory cytokine release following
administration of HD Ads was attenuated. HD Ad DNA was present
at high concentrations in the livers of mice at termination of the
investigation, which indicates that diminished efficacy was a result
of switching off of transgene expression rather than elimination of the
vector from hepatocytes. Alternative transcription control elements,
reduction of immunostimulation by pretreatment with dexamethasone
and polymer modification are being investigated to improve delivery
of anti-HBV RNAi activators by these vectors.
Doesn't Arrowhead Research Corp has a safe delivery platform for RNAi?
Hepatitis B virus (HBV) is hyperendemic to southern Africa,
east and south east Asia where there are approximately 350 million
chronically infected individuals. Chronic carriers have an increased
risk of developing potentially fatal complications of cirrhosis and
hepatocellular carcinoma. Licensed HBV treatments rarely eliminate
the virus from infected individuals, and improvement of HBV therapy
remains a priority. We have previously demonstrated that CMV and
U6 (Pol II/III) expression cassettes that generate artificial antiviral
RNA interference (RNAi) activators can be used to inhibit HBV gene
expression in vivo. Nevertheless, achieving safe and efficient delivery
of these anti-HBV RNAi sequences remains an important objective.
Recombinant adenoviruses (Ads) are amongst the most efficient
hepatotropic gene delivery vehicles, but a drawback of their use is
transient transgene expression and toxicity resulting from induction
of host immune responses. To limit vector immunostimulation, we
have generated RNAi-activating anti-HBV gutless helper-dependent
(HD) Ads. Efficacy against HBV replication was tested in HBV
transgenic mice, which stringently simulate the human condition of
chronic HBV infection. Two days after intravenous administration
of 5×109 recombinant HD Ads to HBV transgenic mice, 80-90%
of hepatocytes were transduced. Markers of HBV replication were
decreased by approximately 95% in animals receiving the HD Ads
and this effect was sustained for 8 weeks without adverse effects.
Compared to unmodified first generation anti-HBV Ads, inhibition
of viral replication was significantly more sustained. Moreover,
acute hepatotoxicity and proinflammatory cytokine release following
administration of HD Ads was attenuated. HD Ad DNA was present
at high concentrations in the livers of mice at termination of the
investigation, which indicates that diminished efficacy was a result
of switching off of transgene expression rather than elimination of the
vector from hepatocytes. Alternative transcription control elements,
reduction of immunostimulation by pretreatment with dexamethasone
and polymer modification are being investigated to improve delivery
of anti-HBV RNAi activators by these vectors.
I communicated with Dr Abdullah Ely few times. According to him, the major stumbling block in RNAi treatment is toxicity. Basically, safe delivery of drugs to the liver. Will take 10 - 15 years to see this new treatment.
Thanks for the information. I went to the website and it was not listed.
The dealt between Gilead and GlobeImmune was for the development of a therapeutic vaccine:
http://www.bizjournals.com/sanfrancisco/blog/biotech/2011/10/gilead-globeimmune-hepatitis-b.html
The following is the tiltle of an abstract delivered at a recent ASCGT conference.
Sustained and Safe Inhibition of Hepatitis
B Virus Replication In Vivo Using Helper-
Dependent Adenovirus Vectors To Deliver Antiviral
RNAi Expression Cassettes
Carol Crowther,1 Mohube B. Mowa,1 Abdullah Ely,1 Patrick
Arbuthnot.1
1Antiviral Gene Therapy Research Unit, University of the
Witwatersrand, Joahannesburg, South Africa.
The dealt between Gilead and GlobeImmune was for the development of a therapeutic vaccine:
http://www.bizjournals.com/sanfrancisco/blog/biotech/2011/10/gilead-globeimmune-hepatitis-b.html
The following is the tiltle of an abstract delivered at a recent ASCGT conference.
Sustained and Safe Inhibition of Hepatitis
B Virus Replication In Vivo Using Helper-
Dependent Adenovirus Vectors To Deliver Antiviral
RNAi Expression Cassettes
Carol Crowther,1 Mohube B. Mowa,1 Abdullah Ely,1 Patrick
Arbuthnot.1
1Antiviral Gene Therapy Research Unit, University of the
Witwatersrand, Joahannesburg, South Africa.
some more info on this-
http://benitec.com/documents/12%2005%2014%20ddRNAi%20-%20The%20Next%20Therapeutic%20Revolutuon.pdf
slide 19 and 41 are of our intrest. Intresting to see Gilead's name there.
http://benitec.com/documents/12%2005%2014%20ddRNAi%20-%20The%20Next%20Therapeutic%20Revolutuon.pdf
slide 19 and 41 are of our intrest. Intresting to see Gilead's name there.
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