New liver cells from replication (=mitosis) doesn't contain cccDNA

[ThomasTu]

@availlant

The other problem with this approach is that it again is sequence dependent mechanism (like antisense and siRNA) and, like cccDNA, the population of integrated HBV DNA will contain many genetic variants. There will be integrants which will escape recognition of the this gene targeting approach.

@Bansah1

My issue with this type of gene editing is the fear that the targeted section is not cut rather a different section is and what could the effect of that be on the person? If I understand, they program this editing technology like scissors to cut the affected part targeted. But what happens if the treatment ends up cutting a different section that was not targeted?

Both great points and definitely issues that need to be really well investigated before wide-spread use.

@lemlem

Good to know this i never imagin with this efficiency still left millions of cccdna, so in that sens after functional cure also do we have this amount of cccdna left ??? If not why not this method should focuse on eliminating inactive ccdna at least will reduce and make it less capable for reactivation .

Dear @lemlem, great question. We know that even with natural clearance of HBV (acute infection), people still have active cccDNA in their liver. This is generally well suppressed by our immune system, but the infection can reactivate if you are put on very strong immunosuppressants that affect B-cells (the producers of antibodies).

Thomas

[lemlem]

@ThomasTu @availlant @Bansah1

Tune therapeutics also start phase1 epigentic based hbv cure , how did you see this method , i understand in this case there no cut and no off target , i am not sure in this case sequence dependent or independent . what type of treatment this is when we compare with ARCUS the one precision use and success rate
https://www.businesswire.com/news/home/20241114651346/en/Tune-Therapeutics-Moves-into-Clinical-Spotlight-with-TUNE-401-A-First-in-Class-Epigenetic-Silencer-for-Hepatitis-B

[ThomasTu]

Dear @lemlem,

Thanks for bringing up this interesting research. This approach is essentially looking to inactivate the HBV DNA using the body’s processes of shutting down gene activity. This effectiveness of this approach would still be virus sequence dependent for the area that is targeted.

We don’t really know what the success rate will be in people until the clinical trials are completed and published.

Thomas

[availlant]

This approach is sequence dependent so will suffer from the same limitations we have already observed with all other approaches like this (siRNA, antisense, ARCUS).

[availlant]

The TUNE platform is Cas9 based…

[lemlem]

thank you both @ThomasTu and @availlant for being active and respond quickly.