Precision Medicine, CRISPR, and Genome Engineering Moving from Association to Biology and Therapeutics

37

Table 2.1

Therapeutic applications of gene editing via AAV combined with engineered nucleases

Disease

Target gene

Target cell/tissue

Nuclease used

AAV serotype used

Modification type

Reference

Note

HIV infection

CCR5

CD4+ T cells

ZFN

rAAV6

Disruption

[^44

]

Donor template only in AAV; nuclease mRNA

Hemophilia B

FIX

Hepatocytes

ZFN

rAAV8

Correction

[^67

]

Cardiovascular/cholesterol homeostasis

PCSK9

Liver/hepatocytes

SaCas9

rAAV8

Disruption

[^51

]

DMD

Dmd

Muscle

SpCas9

rAAV9

Exon excision

[^53

]

Muscle

SaCas9

rAAV9

Exon excision

[^55

]

Muscle

SaCas9

rAAV8

Exon excision

[^56

]

Metabolic disease

OTC

Liver/hepatocytes

SaCas9

rAAV8

Correction

[^54

]

Hepatitis B infection

HBV polymerase

HepAD38 cells

ZFN

rAAV2

Disruption

[^68

]

Tyrosinemia

Fah

Hepatocytes/liver

SaCas9

rAAV8

Correction

[^69

]

Donor template only in AAV; nuclease mRNA

2 Combining Engineered Nucleases with Adeno-associated Viral Vectors...