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RESEARCH

INNOVATIVE SAFE HARBORS

The RhD locus is disrupted in a substantial portion of the general population.  This gene locus encodes for the RhD blood antigen.  Individuals in which the RhD locus is disrupted are clinically classified to have the Rh-negative blood type.  No phenotypic consequence has yet to be associated with the loss of the RhD gene; therefore this location in the genome is prime for gene addition.  These studies will confirm the utilization of the RhD locus as a safe harbor extending the application of this study beyond hemophilia A.

IDLV DONOR DELIVERY

Viral delivery vectors are ideal for gene delivery having the ability to transduce both dividing and non-dividing cells.  However, only integrating lentiviral vectors have enough carrying capacity to contain a large transgene as FVIII.  Yet, lentiviral vectors integrate in an uncontrollable manner and can cause genomic instability.  The integrase deficient lentiviral vector, on the other hand, does not contain the gene for integrase, the enzyme that allows for genomic incorporation of viral DNA.  Therefore, IDLV offers the newest means to enhance gene editing.  Because IDLVs are based on lentiviruses, they can transfer large genetic loads efficiently and transduce a large variety of dividing and non-dividing cells, all without disrupting the integrity of the genome.

PLATELET EXPRESSION OF FVIII

As an active locus in the hematopoietic system, the vWF locus is prime for HPFVIII expression.  In addition, the expression of HPFVIII from the vWF locus provides a treatment option for the substantial portion of hemophilia patients that have developed inhibitors to recombinant fVIII.  vWF is contained within α granules until platelets become activated.  This unique expression characteristic would prevent HPFVIII from being accessible to inhibitors, which circulate in the bloodstream, until blood vessels rupture causing platelets to activate.   Therefore, HPFVIII would be safely sequestered in the α granules of platelets until physiologically necessary.