CDK9 Gene Editing    

The CDK9 (cyclin-dependent kinase 9) gene encodes two subtypes of protein, the major 42 kDa protein and the minor 55 kDa protein. CDK9 plays a key role in controlling global (non-ribosomal) transcription, especially including gene expression regulated by super-enhancers, and a large number of DNA regulatory elements ("enhancers") that drive cell identity-related gene transcription, including MYC and apoptosis regulator MCL-1. MYC is involved in cells growth and cell cycle progression downstream proto-oncogenes. CDK9 also appears to be involved in several physiological processes of extra-transcribed cells, including differentiation, apoptosis, and signal transduction.

Figure 1: Regulation of transcription by CDK9. (Muhammed H Rahaman. 2016)

Functional details of CDK9

• CDK9 is mainly associated with cyclin T1, forming a positive transcription elongation factor b (p-TEFb) complex. P-TEFb is responsible for phosphorylation of the carboxy-terminal domain of RNA Pol II, thereby stimulating transcription, and mRNA maturation regulation.
• CDK9 is a kinase of the TAK complex (Tat-associated kinase complex) and binds to the Tat protein of HIV, suggesting that CDK9 may play a role in the AIDS process.
• CDK9 is involved in many types of cancer by recruiting BRD4-dependent p-TEFb for transcription of the MYC gene. This may have clinical and therapeutic implications for these tumor types.

Target CDK9 therapy

Given that CDK9 is a kinase, it is considered to be a relatively easy target for drug discovery and provides a pathway for indirect targeting of MCL-1 and MYC, while MCL-1 and MYC are considered to be more current challenging targets in drug discovery.

Table1. List of CDK9 inhibitors that reached preclinical or clinical development. (Muhammed H Rahaman. 2016)

Compound	Developmental stage
CDKI-73	Preclinical
Dinaciclib	Multiple clinical trials for hematologic and solid tumors
Flavopiridol	Phase II clinical study against different solid tumors and leukemia (the only CDK9 inhibitor in clinical trial in prostate cancer)
LY2857785	Preclinical
P276-00	Phase I/II clinical trials for pancreatic cancer, multiple myeloma, mantle cell myeloma, breast cancer and melanoma
Roscovitine	Phase I for advanced solid tumors, Phase II studies for Cushing's disease and cystic fibrosis
SNS-032	Phase I clinical trials in advanced solid tumors and advanced B-lymphoid malignancies
TG02	Phase 1 clinical trials in advanced hematological malignancies

CDK9 Gene Editing Service

CRISPR/Cas9 Platform^CB provides comprehensive CRISPR/Cas9 gene editing services and products to a wide range of genomics researchers. Based on our platform, we can help you effectively regulate your target genes editing in vivo and in vitro using the CRISPR/Cas9 system.

• Our CDK9 gene editing services include

Mutation via CRISPR Gene Editing

We are able to perform specific DNA deletions, mutations or substitutions to study gene function with CRISPR/Cas9 gene editing technology with high precision. Available services:
➢ Knockout
➢ Point Mutation
➢ Conditional knockout/knock-in
➢ Floxed allele insertion

Mark by CRISPR gene editing

Using the CRISPR/Cas9 gene editing technology, CRISPR/Cas9 Platform^CB is able to tag your genes at the endogenous locus and visualize them with fluorescent proteins or immune-tags for biochemical studies. Available services:
➢ Fluorescent tag
➢ Immuno-tag
➢ Custom tags and combinations are also available

CRISPR/Cas9 Platform^CB has more than a decade of experience in integrating CRISPR/Cas9 technology into more than 200 different cell lines, including those that are easy to transfect and those that are difficult to transfect. We also successfully implemented the CRISPR/Cas9 gene-edited in animal models, which has been well recognized by customers.

• Models we offered

Blood Lineage Cells	RAW264.7, HMC1.2, K562, U937 etc.
Cancer Cell Lines	HEK293, HEK293T, Hela, MCF7, Neuro2a, HepG2, U87, etc.
Stem Cells	iPSC
Other Cell Lines	NIH3T3, MCF10, HEME, SW10 etc.
Animal models we offered	mouse, rat, rabbit, zebrafish, C. elegans, etc.

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