Paragraph 3 - Targeting BCL11A and Reactivating HbF

Paragraph 3 - Targeting BCL11A and Reactivating HbF layout

what the design focuses on
    what BCL11A is
    what BCL11A does
    mechanism of action involves
    CRISPR cas 9 targeting
    disrupting the enhancer
    reducing repression
    replacement of HbS

Paragraph 3 -

Targeting BCL11A and Reactivating HbF

Paragraph 3 - Targeting BCL11A and Reactivating HbF 1

what the design focuses on

Paragraph 3 - Targeting BCL11A and Reactivating HbF 2

what BCL11A is

Paragraph 3 - Targeting BCL11A and Reactivating HbF 3

what BCL11A does

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mechanism of action involves

Paragraph 3 - Targeting BCL11A and Reactivating HbF 5

CRISPR cas 9 targeting

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disrupting the enhancer

Paragraph 3 - Targeting BCL11A and Reactivating HbF 7

reducing repression

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replacement of HbS

Paragraph 3 - Targeting BCL11A and Reactivating HbF what the design focuses on

the BCL11A gene,

Paragraph 3 - Targeting BCL11A and Reactivating HbF what BCL11A is

TF

Paragraph 3 - Targeting BCL11A and Reactivating HbF what BCL11A does

normally represses HbF expression shortly after birth to facilitate the "fetal switch" to adult haemoglobin.

Paragraph 3 - Targeting BCL11A and Reactivating HbF full sentence

The design focuses on the BCL11A gene, a transcription factor normally represses HbF expression shortly after birth to facilitate the "fetal switch" to adult haemoglobin.

Paragraph 3 - Targeting BCL11A and Reactivating HbF mechanism of action involves

CRISPR cas 9 targeting
    disrupting the enhancer
    reducing repression
    replacement of HbS

Paragraph 3 - Targeting BCL11A and Reactivating HbF CRISPR cas 9 targeting What does the therapy use and why

uses a guide RNA (gRNA) to direct the Cas9 nuclease to an erythroid-specific enhancer of the BCL11A gene.

Paragraph 3 - Targeting BCL11A and Reactivating HbF disrupting the enhancer what do they use

Cas9

Paragraph 3 - Targeting BCL11A and Reactivating HbF disrupting the enhancer what does cas9 do and where

Cas9 induces double-strand breaks at this enhancer

Paragraph 3 - Targeting BCL11A and Reactivating HbF disrupting the enhancer specific location

at motifs enriched for GATA1 and TAL1 transcription factor binding.

Paragraph 3 - Targeting BCL11A and Reactivating HbF disrupting the enhancer full sentence

Cas9 induces double-strand breaks at this enhancer, specifically at motifs enriched for GATA1 and TAL1 transcription factor binding.

Paragraph 3 - Targeting BCL11A and Reactivating HbF reducing repression what do these mutations do

reduce BCL11A expression specifically in erythroid cells.

Paragraph 3 - Targeting BCL11A and Reactivating HbF reducing repression why do they reduce in eryhtroid cells

Because BCL11A is no longer present at high levels to repress the promoters of the HbF coding genes (HBG1 and HBG2)

Paragraph 3 - Targeting BCL11A and Reactivating HbF reducing repression what is reactivated

HbF production is reactivated.

Paragraph 3 - Targeting BCL11A and Reactivating HbF reducing repression sentence 1

These mutations reduce BCL11A expression specifically in erythroid cells.

Paragraph 3 - Targeting BCL11A and Reactivating HbF reducing repression sentence 2

Because BCL11A is no longer present at high levels to repress the promoters of the HbF coding genes (HBG1 and HBG2), HbF production is reactivated.

Paragraph 3 - Targeting BCL11A and Reactivating HbF replacement of HbS what happens to the edited stem cells

are re-infused into the patient after myeloablative conditioning

Paragraph 3 - Targeting BCL11A and Reactivating HbF replacement of HbS what do the stem cells produce

red blood cells with high levels of HbF,

Paragraph 3 - Targeting BCL11A and Reactivating HbF replacement of HbS what does hbf prevent

which prevents the sickling of cells.

Paragraph 3 - Targeting BCL11A and Reactivating HbF replacement of HbS full sentence 1

Once the edited stem cells are re-infused into the patient after myeloablative conditioning,

Paragraph 3 - Targeting BCL11A and Reactivating HbF replacement of HbS full sentence 2

they produce red blood cells with high levels of HbF, which prevents the sickling of cells.