Dr David Bloom (Univ of Florida) and Bryan Cullen (Duke Univ

Dr David Bloom (Univ of Florida) and Bryan Cullen (Duke Univ) on their gene editing "cure" approach to HSV.
Reading this link will tell much of what's going on with them.


Update on HSV Research

We have recently extended our efforts to cure HSV infections by developing DNA editing enzymes as potential HSV treatments. I refer to these as “smart bombs” that can cleave the HSV-1 genome, and destroy the latent virus, if delivered to latently infected neurons using viral vectors. The only viral vectors that really make sense at this point are based on adeno-associated virus (AAV), which has been successfully used in gene therapy trials in humans. The big advantage of AAV is that you can get very high levels of virus—up to 10 billion infectious units per milliliter—and the Bloom lab has clearly shown, using an AAV that expresses green fluorescent protein (gfp), that he can infect essentially every single neuron in the trigeminal ganglia where HSV-1 establishes latency. The problem is that the AAV packaging size, that is the amount of DNA that it can fit into its viral capsid, is only ~4,600 bp.

Our initial efforts to use gene editing to destroy HSV-1, while very successful, used either transcription activator-like endonucleases (TALENs) or bacterial editing enzyme of the CRISPR/Cas9 family, derived from Streptococcus pyogenes (SPy), both of which work well but have size issues. The TALENs work as heterodimeric DNA binding and cleavage enzymes and, while AAV can package one TALEN, it cannot package two. The SPy Cas9 gene is so large that even on its own it is too big for AAV.

So, my long-term collaborator David Bloom and I have taken two approaches. On the one hand, we have generated AAVs that express one or the other TALEN and have generated viral stocks of each. We intend to mix these two stocks and then use the mixture to infect the trigeminal ganglia in mice at high levels of virus such that each neuron should be infected by both AAVs, allowing expression of the TALEN heterodimer and HSV-1 cleavage. These experiments are now in progress in latently HSV-1 infected mice in the lab of Dave Bloom at the University of Florida.

The second approach we have taken is to identify Cas9 proteins encoded by other bacteria that are highly active but small enough to fit into AAV. The one we are currently focused on is derived from Neisseria meningitidis (NMe). This Cas9 gene is only 3,200 bp in size, well below the 4,600 bp cutoff, and works well. Nevertheless, we have now cloned this into AAV, where it is well expressed, and sent it off to Dave Bloom to put into mice. While these are being tested, we are also testing Cas9 genes we have isolated from other bacteria and we are in the process of establishing a collaboration with a biotech company that focuses on the use of Cas9-derived DNA editing enzymes in the treatment of human disease. I have visited their headquarters and they have stated that they are enthusiastic about working with us on the goal of using Cas9 to cure HSV-1 and, especially, HSV-2. Hopefully, this will allow us to move this project along more rapidly, using new resources provided by this company.

So, some progress has been made but we haven’t quite achieved full success. I’m very enthusiastic about the approach we are pursuing, because I really think this could be a way to actually destroy latent HSV genomes and lead to the cure we have all sought. I hope the next update will include the statement that we can at least cure mice! Once that is achieved, I think things will really start to move forward.

12 Hearts

Amazing share!

Yes! Thanks! What do you guys think about that? Will happen his time? Any guestimates on how long would it take for us to actually be able to get a cure? 5 years?

I would say within the next 5-10 years.

1 Heart

That's awesome. Fingers crossed this one or the DRACO cure happens that fast.

1 Heart

Here's a link showing the compounds that David Bloom and Bryan Cullen are using. It shows how they seek out the programmed pieces of DNA that they will snip and how they don't inappropriately snip/edit the wrong DNA. so neat! ^_^

This is amazing. I hope to see a cure one day.

1 Heart

This is the best news I've read in a really long time. I pray they develop a cure!!!!!!

1 Heart

There has been lot of companies working on to make vaccine to cure herpes. Most of the researchers are confident about find a herpe cure within next 20 yrs because going to all clinical phases and receiving FDA approval will take at least 8-10 yrs.

So its expected that within next 20 yr we'll have vaccine in market approved by FDA.

1 Heart

I will be excited when it happens and now just hope for the future there is a cure for others.

1 Heart

I hope the cure would be offered to us as well. 20 years from now I'll be in my 30's lol so I really really hope so