Gene Therapy in ADA-SCID

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Questions and Answers

What is the primary mechanism by which siRNA inhibits specific genes in genetic diseases?

By activating the gene's promoter region

By binding to the gene's transcription factor

By inhibiting the gene's transcription elongation

By degrading complementary mRNA (correct)

Which enzyme is responsible for processing and cleaving longer double-stranded RNA into siRNAs?

RNase H

Polymerase

Dicer (correct)

Helicase

What is the role of the RISC complex in the RNAi pathway?

To inhibit the action of Dicer

To bind and separate siRNA strands (correct)

To synthesize siRNA

To degrade siRNA

What guides the RISC complex to target mRNA during the RNAi pathway?

The anti-sense single-stranded siRNA component Signup and view all the answers

Why are carriers necessary for the effective pharmacological use of siRNA?

To deliver the siRNA to its intended site of action Signup and view all the answers

What is the normal biological function related to the RNAi pathway?

Defence against viruses and mobilisation of transposons Signup and view all the answers

What are the two major categories of delivery systems for siRNA?

Viral vectors and non-viral vectors Signup and view all the answers

What is the primary function of cell penetrating peptides (CPPs) in siRNA delivery?

To cross the plasma membrane and deliver siRNA Signup and view all the answers

What type of delivery system includes liposomes and solid lipid nanoparticles?

Lipid-based delivery system Signup and view all the answers

What is the primary goal of siRNA therapy in cancer treatment?

To develop innovative medicine for incurable diseases Signup and view all the answers

What is the current limitation of siRNA delivery systems for cancer therapy?

Most approaches are limited to cell cultures in the laboratory Signup and view all the answers

What is the consequence of siRNA off-target gene regulation?

Suppression of genes other than the desired gene target Signup and view all the answers

What is the primary application of siRNA in cancer therapy?

To target dominant oncogenes in cancer cells Signup and view all the answers

What is the current progress in siRNA delivery systems discussed in the text?

Liver, breast, prostate, and lung cancers Signup and view all the answers

What are two important features of AAV that attracted the attention of gene therapy researchers?

It does not appear to cause any disease in humans and tends to remain inactive in the absence of a helper virus Signup and view all the answers

What is the traditional treatment for ADA-SCID?

Bone marrow transplant and weekly injections of ADA Signup and view all the answers

Why was gene therapy explored as a treatment option for ADA-SCID?

Because transplants often fail and enzyme therapy is ineffectual in many patients Signup and view all the answers

What is the main challenge in creating an HIV vaccine?

The inaccuracy of the replication machinery of the virus Signup and view all the answers

What is the goal of current anti-HIV-1 gene therapy?

To reduce plasma viral load and improve patient quality of life Signup and view all the answers

What is the strategy to overcome the great variability of HIV-1?

To combine the use of different ribozymes with different specificities Signup and view all the answers

What are ribozymes designed to target?

Different HIV-1 genes Signup and view all the answers

What is the significance of understanding the HIV-1 life cycle?

It is necessary for designing anti-HIV-1 gene therapy Signup and view all the answers

What is the primary cause of sickle cell anemia?

A mutation in the gene that helps make hemoglobin Signup and view all the answers

What is the significance of early detection and intervention in genetic diseases?

It enables timely intervention and management Signup and view all the answers

What is the primary goal of gene therapy?

To provide personalized treatments tailored to individual genetic profiles Signup and view all the answers

What is the difference between in vivo and ex vivo strategies in somatic cell gene therapy?

In vivo techniques deliver the target gene to the desired cell type within the patient, while ex vivo strategies manipulate cells out of the body and then reimplant them into the patient Signup and view all the answers

Why are stem cells often used in somatic cell gene therapy?

Because they are actively dividing and can be easily removed Signup and view all the answers

What is the advantage of liposomes as vectors in somatic cell gene therapy?

They are non-toxic and non-immunogenic Signup and view all the answers

What is the mechanism of liposome-mediated gene transfer?

The liposome bilayer fuses with the plasma membrane and releases the DNA into the cell Signup and view all the answers

What is the primary function of DNA helicase during DNA replication?

To unwind the DNA molecule Signup and view all the answers

What is the purpose of creating an RNA primer during DNA replication?

To initiate the synthesis of new DNA nucleotides Signup and view all the answers

In which direction does DNA polymerase add nucleotides to the leading strand during DNA replication?

5' to 3' direction Signup and view all the answers

What is the main difference between the leading strand and the lagging strand during DNA replication?

The leading strand is synthesized continuously, while the lagging strand is synthesized in short fragments Signup and view all the answers

What type of enzyme is DNA primase?

An RNA polymerase Signup and view all the answers

What is the role of DNA polymerase III in prokaryotes?

To synthesize the leading strand Signup and view all the answers

Why is it necessary to remove the RNA primer from the DNA molecule?

Because RNA primers are not part of the final DNA product Signup and view all the answers

What is the relationship between the direction of DNA synthesis and the direction of DNA polymerase activity?

DNA synthesis occurs in the 5' to 3' direction, and DNA polymerase activity occurs in the same direction Signup and view all the answers

Study Notes

RNA Interference (RNAi)

RNAi is a mechanism by which double-stranded RNA (dsRNA) induces gene silencing by targeting complementary mRNA for degradation
RNAi has revolutionized the way researchers study gene function and has the potential to treat genetic diseases

Mechanism of RNAi

The first step of RNAi involves processing and cleavage of longer double-stranded RNA into siRNAs by the enzyme Dicer
siRNAs are bound by a multiprotein component complex referred to as RISC (RNA-induced silencing complex)
Within the RISC complex, siRNA strands are separated and the strand with the more stable 5'-end is typically integrated into the active RISC complex
The antisense single-stranded siRNA component guides and aligns the R ISC complex on the target mRNA

Challenges with siRNA-Based Therapeutics

Delivering siRNA to its intended site of action requires 'carriers' that can deliver the siRNA effectively
Two major categories of delivery systems for siRNA: viral vectors and non-viral vectors

siRNA Delivery Systems

Polymer-mediated delivery systems: used for plasmid DNA and recently for siRNA
Peptide-based delivery systems: cell-penetrating peptides (CPPs) have been observed to cross the plasma membrane by themselves
Lipid-based delivery systems: various lipid-based delivery systems have been developed for in vivo application of siRNA, including liposomes and solid lipid nanoparticles

Delivery of Therapeutic siRNA in Cancer

siRNA has provided new opportunities for the development of innovative medicine to treat previously incurable diseases such as cancer
siRNAs have been designed to target dominant oncogenes, viral oncogenes involved in carcinogenesis, or malfunctionally regulated oncogenes
Therapeutic siRNAs have been investigated for silencing target molecules crucial for tumor-host interactions and tumor resistance to chemotherapy or radiotherapy

Off-Target Effects

siRNA off-target gene regulation can lead to dangerous mutations of gene expression and unexpected consequences
Gene expression profiling of siRNA studies has revealed the suppression of genes other than the desired target

Sickle Cell Anemia

Caused by a point mutation where A (adenine) is replaced by T (thymine) in the gene that helps make hemoglobin
A genetic disorder that can be detected early, allowing for timely intervention and management

Gene Therapy

Vectors for somatic cell gene therapy: in vivo and ex vivo strategies
Liposome vectors: advantages include being non-toxic and non-immunogenic, but gene transfer is highly inefficient and expression is transient

HIV-1 Gene Therapy

HIV-1 infection and its associated disease, acquired immunodeficiency syndrome (AIDS), have driven the development of anti-HIV-1 gene therapy
Ribozymes have been designed to specifically target different HIV-1 genes, aiming to reduce plasma viral load and improve patient quality of life

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Description

This quiz explores gene therapy as a treatment option for ADA-SCID, a severe immune disorder. It discusses the benefits of AAV in gene therapy and the limitations of traditional treatments.