"I could be mistaking who expressed it.  All that I recall is that a concern was expressed about the long-term effects / unknown consequences of some sort of virus delivery, perhaps it was in relation to the CRISPR-cas9 approach?  Spark's virus delivery method reminded me of this.  Maybe the two aren't comparable to begin with."

It might have been me. This era of gene targeted therapies is truly remarkable. There's Ionis Pharmaceuticals' antisense oligonucleotide technology that can target specific mRNAs to prevent expression of the encoded protein, with some therapies already having FDA approval,. There's Alnylam's RNA interference (RNAi) pipeline that targets specific mRNAs (distinct mechanism from antisense oligos) to prevent expression of the encoded protein, with one therapy FDA approved and others in late clinical development (including a PCSK9 targeted inclisiran). There's Moderna's up and coming mRNA based pipeline of drugs that are still in early clinical development. All of the above are "transient" therapies that do not alter the DNA but only modulate the expression of the encoded mRNA or protein. So these types of therapies above would need to be given repeatedly as their effects wane. 

On the flip-side, there's gene editing technology (i.e. CRISPR) than has potential to alter the genomic DNA in order to correct a genetic mutation, inactivate a gene, enhance a gene function, etc. Unlike the transient therapies mentioned above, CRISPR gene editing is more long-term. Once the cell's DNA is edited, the mRNA encoded by that altered DNA will reflect this change until this cell dies. Since most somatic (non-germline) cells can still divide, somatic cell division will perpetuate this CRISPR-mediated genetic change if in vivo editing is performed. And of course there may be concerns about in vivo editing eliciting germline changes that may edit the genetic info of the sperm and eggs. So obviously, CRISPR tech comes with concerns about long-term safety, especially if the editing is done in vivo. 

Then there is adeno-associated virus (AAV), which is more of a vector, or a vehicle to carry or transmit the genetic information. A key advantage of AAV is that it has been altered in a way that the viral particles cannot replicate and so there is minimal concern about the virus being able to persist or infect others after infecting the host cells. Another key advantage is that AAVs give rise to long-term expression of the encoded gene either by existing as an "episome" inside the cell or actually integrating into the human host cell DNA. So theoretically, these AAV approaches are a "once and done" therapy that gives rise to long-term expression. AAV's are quite versatile. They can be engineered to express a gene of interest to increase gene expression, express a small hairpin RNA (shRNA....a form of RNAi) to decrease expression of a gene, encode the CRISPR-Cas9 enzyme to elicit CRISPR gene editing, or even encode a therapeutic antibody. Furthermore, these genes, shRNAs or antibodies encoded by these AAVs can be put under certain control elements to only allow expression in a certain tissue type via use of tissue-specific promoters. So AAVs are very versatile vectors, but the long-term expression does present some long-term safety concerns.

There's also the issue of tissue distribution of the virus. For local administration, such as intramuscular injection, eye delivery (i.e. Spark's Luxturna), intrathecal injection, etc. there is minimal concern of the virus infecting tissues outside of the delivery area. However, if the AAV is delivered systemically via intravenous injection, then there may be concerns about widespread AAV infection throughout the body. In general, AAVs have a hard time crossing the blood brain barrier (BBB), which in the past has made application of intravenous AAV for neurological applications difficult unless a very high and dangerous dose of AAV is used (dangerous because it can elicit a severe immune response). However, there are some newer generations of engineered AAVs that are better able to cross the BBB w/o this high dosing. This is where Voyager's AAV tech comes into play due to their engineered AAV capsid protein that is better able to penetrate the BBB.

The era of gene targeting therapies is upon us. Very exciting.

BearDownAZ