Cross BBB to deliver genetic therapeutics to CNS: AAV vs...

Cross BBB to deliver genetic therapeutics to CNS: AAV vs ADC

Yesterday I came across an article (dated 19 Oct 2022) about a novel AAV approach allows gene therapies to cross the blood-brain barrier. It says most AAVs identified to date are not considered efficient enough for use in clinical settings, and now researchers at Brigham and Women’s Hospital have unveiled a novel AAV variant that (when tested in preclinical models) was markedly more efficient than previous delivery vehicles, which demonstrates that AAVs could provide a valuable tool for developing systemic gene therapies against glioblastoma and other diseases where CNS delivery is required.

Above article piqued my curiosity so I did some research on this technology and found there are plenty of AAV related articles reporting successful test results of their AAV penetrating BBB. However, to date using AAV has some disadvantages such as low crossing BBB efficiency, very small gene payload, and high level of manufacturing difficulties, and so on.

According to Patrys Ann last Oct, PAT-DX3 can effectively cross the blood-brain in healthy animals, opening potential new pathways to use deoxymabs to deliver small molecule therapeutics and gene editing technologies for various neurological conditions, which is quite unique in the heated ADC (Antibody Drug Conjugate) world. PAT-DX3 appears to outperform antibodies specifically developed by other companies for the delivery of payloads to brain tissue. None of these other antibodies are able to deliver their payloads into the cell and the cell nucleus.

Early this month, Takeda (武田薬品工業株式会社), a Japanese pharma giant with over 240 years of history, has confirmed it is ending discovery and preclinical work in AAV gene therapy. Just one year ago, in February 2022, Takeda signed off on a $2B deal aimed at bypassing AAV roadblocks on the way to gene therapy 2.0.

Why did Takeda make such a surprising sharp turn? One possible reason is that there has appeared a far more superior technology out there, which could make their early-stage AAV gene therapy research work hopeless and therefore meaningless.

IMHO, DYOR