Question

Is the CRISPR-Cas9 system more similar to the human innate or adaptive immune system? Briefly explain your answer

Answer 1

• CRISPR is Clustered Regulatory Interspaced Short Palindromic Repeats.
• CRISPR associated –Protein 9 nuclease Caspase (Cas-9) is used as a molecular tool for editing of genomes.
• It acts in a similar manner as genetic engineering or construction of GMO (genetically modified organism).

CRISPR/ Cas9 system has components that help in their gene editing:

1. crRNA- guide RNA (g RNA) and sequence recognizing trac rRNA

2. trac rRNA- in stem-loop structure, bind (to be activated) to crRNA

3. Cas9-active form have nuclease, nick formation, single strand/double strand breaks, editing.

4. sgRNA-single guide RNA-with combination of other components

• The recognition point in the target DNA is designated as the PAM (Proto-spacer adjacent motif). The sequence is at the 3’ end of the target sequence(about 20 nucleotides)
• The CAS-9 component recognizes the PAM sequence. CAS- 9 then mediates unwinding or DNA and nick formation (nick is formed at about 3 bp upstream of the PAM).
• The CAS-9 recognition is aided with crRNA.
• The gRNA thus, associated with the crRNA act as recognition sequence, changing of which alters the recognition capabilities of the CAS-9.
• The antigenic determinant sequence of a pathogen may be introduced in thid manner.
• This initiates an immune response.

• On first exposure of antigens, acquired immunity requires time to generate an immune response. Once the immune response identifies the antigen, it exhibits an “immunological memory”. On interaction with antigens, lymphocytes differentiate in effector cells (effector B cells or T cells) ad memory cells. Thus, on subsequent exposure to the same antigen quicker and accelerated immune response.

• Thus, the antigenic sequence introduced through CRISPR will ilicit acquired immune response.