It has a payload size limitation, the drug cargo cannot exceed the size of the virus itself. That immediately eliminates itself from carrying more modern and complex drug cargos.
It may cause an immunogenicity reaction in the body, apart from adverse viral side effects which could be serious for immunocompromised patients, subsequent dosage could have a diminishing efficacy.
You would be dead wrong if you think one AAV virus + drug cargo would only enter one cell. Uneven distribution and penetration into cell is the most detrimental attribute of AAV. It has been found that some cells received as high as 10X the desired dosage, if a cell is overdosed, toxicity would start to kick in.
Luxturna is a case in point. It was FDA approved on 18.12.2017 to treat "biallelic RPE65 mutation-associated retinal dystrophy". But general acceptance is plagued by toxicity due to its 10-fold uneven spread over cells. Patients also need to be treated with a short course of oral prednisone to limit the potential immune reaction. Most common adverse reactions included eye redness (conjunctival hyperemia), cataract, increased intraocular pressure and retinal tear.
PYC's is extremely happy to confirm that their CPPs have produced very even distribution and penetration, making dosing very accurate and keeping toxicity to a minimum. Is Luxturna a competitor, absolutely not!
PYC's CPP vs Others'
CPP is not new and a number of companies do have their own CPPs at their disposal. However,PYC has a library of over a billion to choose from. They have also developed their own platform for fast selection of suitable CPPs so it could be narrowed down to a handful for further scrutiny.
High efficiency and low toxicity in carrying drug cargo into cell are the major distinctions of PYC's CPP from the others.For VP-001, PYC is using only 1.6 micro gram per eye. That is 0.000 0016 gram, which is 1,000X less than the mg (miligram) that is common in our medications. So far, PYC has seen good target engagement in the eye across 1.6, 3.2, and 6.4 micrograms with no major increase in toxicity markers, and then when injected systemically there were no elevation in toxicity markers at 30mg/kg!
(20min delay)