A program of work has been defined by CHOP to explore feasibility of treatment of H-ABC using three possible approaches:
1) Reduce the expected toxicity to cells from the mutated tubulin by using an approach that captures RNA before it becomes proteins (antisense oligos or ASOs).
2) Out compete the mutant tubulin through overexpression of wild type (ie correct) TUBB4A in the cell. Dr. Vanderver will be testing if this approach is successful in her animal and cell models in the lab.
3) Correct the mistake in the tubulin gene through a highly novel gene editing approach that can correct spelling mistakes in genes (using CRISPR to correct the mutation at the DNA level for H-ABC).
We are very happy to announce that CRISPR expert at Harvard/MIT, Professor David Liu will be working with the research team at CHOP. Professor Liu’s work is highly prominent in the field having pioneered the use of engineered CRISPR Cas variants with improved specificity and targeting ability. The advantage of this approach is that it brings a truly cutting-edge technology to treat H-ABC.