The AAV therapeutic approach for various central nervous system (CNS) illnesses has been rapidly growing. Unfortunately, existing present technologies utilize AAV administration that is injected locally into the brain. This process requires a high level of expertise and is not applicable in more diffused brain targets like cortex and stiratum. 
Systemic administration of AAV vectors through intravenous injection provides little efficacy in brain-related treatments, because of two reasons: (1) systemically administered AAV cannot pass through the blood-brain barrier (BBB), and (2) there is high accumulation of AAV in off-target organs such as the liver.
Using the mouse as a model system, recent attempts to genetically engineer recombinant AAVs that can penetrate the BBB, resulted in recombineered AAVs that delivered genetic cargo into the brain 
This was successful only in mice, and not in humans.  
A receptor protein on mouse brain endothelial cells that binds to and then mediates entry of the recombinant AAV into the brain was identified as the membrane protein Ly6a. This protein exists only in mice. Unfortunately, the mouse Ly6a protein does not exist in humans and till now the human homolog to mouse Ly6a was unknown.
It is obvious that to treat human neurological disorders with genetically recombineered AAV, first demands the identification of the human homolog to the mouse Ly6a. This will enable the generation of recombineered AAV that can pass through the human BBB and deliver therapeutic cargo into the human brain.
We have done just that. We have identified the human homolog to the mouse Ly6a. This human homolog has been designated, by the HUGO Gene Nomenclature Committee, as LY6S.
What this discovery means is that we can now generate recombinant AAV that will efficiently transfer genetic information into the human brain by binding to the LY6S protein, the human homolog to mouse Ly6a.
Screening for AAV variants that target human LY6S using transgenic mice will provide for AAV treatment in humans, that following systemic administration can pass through the BBB and deliver therapeutic cargo into the human brain. This will be the only systemically administered AAV available in the market for the treatment of humans.

APPLICATIONS
Screening for AAV variants that target human LY6S leading to systemically administered AAV treatment introducing therapeutic genes into the human brain
• LY6S proteins may serve as receptors for additional pathogenic viruses, thus leading to novel anti-viral therapeutic strategies 
• Targeting cancer cells bearing LY6S cell surface proteins

STATUS
US Provisional patent 

REFERENCES
LY6S, a New Interferon-Inducible Human Member of the Ly6a Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance 
Authors: Moriya Shmerling, Michael Chalik, Nechama I. Smorodinsky, Alan Meeker, Sujayita Roy, Orit Sagi-Assif, Tsipi Meshel, Artem Danilevsky, Noam Shomron, Shmuel Levinger, Bar Nishry, David Baruchi, Avital Shargorodsky, Ravit Ziv, Avital SarusiPortuguez, Maoz Lahav, Marcelo Ehrlich, Bryony Braschi, Elspeth Bruford, Isaac P. Witz and Daniel H. Wreschner
 doi: https://doi.org/10.1101/2021.1…