By: Jack Liao- HOSTOS- Lincoln Academy of Science

Jingwei Zhang- H.S. for Dual Language and Asian Studies

Gabriell Copeland- Eagle Academy For Young Men

Mentor: Professor Thomas Brennen

Facility: Bronx Community College

Function of RNAi

Potential, Unsolved Problems and Future Research

REFERENCE

Discovery and Introduction of RNAi

What is DNA?

Deoxyribonucleic acid (DNA) is a nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life, and many viruses.DNA never leaves the Nucleus.

RNARibonucleic acid (RNA) is a single-stranded nucleic acid which is transcribed from the base sequence of DNA.

Double-stranded RNA (or dsRNA) is RNA with two complementary strands which forms the genetic material of some viruses. It acts as a trigger to initiate the process of RNA interference and is present as an intermediate step in the formation of siRNAs (small interfering RNAs).

dsRNA

An Unusual Experience with Unexpected Results

In 1990, scientists in the US and the Netherlands experimented with petunia plants by introducing “Extra” genes coded for purple pigmentation to increase the color purple in the plants. But instead, a non-pigmented petunia was created. What happened?

What is RNAi?

RNA interference (RNAi) is a mechanism in molecular biology whereby the presence of certain fragments of double-stranded RNA (dsRNA) interferes with the expression of a particular gene which shares a homologous sequence with the dsRNA.

A Double-Stranded RNA of 200 or more bases is introduced into the cell.

RNAi activates.

An RNase III enzyme called Dicer, chops the double-stranded RNA into small interfering RNAs (siRNAs) of 20 or so bases.

The siRNAs then are bound to the RNA-Induced Silencing Complexes (RISC) where the siRNAs are unwound.

Using RNAi, we’re be able to turn off genes by adding extra copies or similar genes to the cells.

With this, the potentials are enormous:

•Cures for Cancer and AIDS may become available.

•Silencing of non-desired genes.

•Human-Control gene expressions.

Cancer

Cancer often involves mutant genes that promote uncontrolled cell growth. In the last few years, researchers have silenced more than a dozen known cancer-causing genes with RNAi. With RNAi, Cancers are preventable and curable.

HIV

As soon as RNA interference was discovered in human cells, scientists began exploring how it could be recruited to battle HIV. By late 2002, Phillip Sharp and colleagues at MIT announced they could interrupt various steps in the HIV life cycle with RNAi molecules.

•At the age of 78, Markey Russell was diagnosed with Macular Degeneration, a genetic disease contributing to the excessive growth of blood vessels which can burst and destroy her vision.

•In an effort to work with the RNAi mechanism, Doctors injected dsRNA into Russell’s eye, signaling grown of blood vessel, in terms, hoping the homozygous genes would be destroyed.

•The outcome is promising. Mrs.Russell can see more clearly now.

Challenges and Future Research

•Finding the function for each of the thousands of specific genes in the human genome.•Better understanding of the RNAi mechanism.•Utilizing the full potential of RNAi applications.•Using RNAi in the treatment and cure of diseases.

NOVA: ScienceNOW. 2005. 17 July 2006 <http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html>

Ambion: The RNA Company. 2006. 17 July 2006 <http://www.ambion.com/techlib/append/RNAi_mechanism.html>

Wikipedia: The Free Encyclopedia. David D. 2006. 18 July 2006

<http://en.wikipedia.org/wiki/Rnai>

Dr. Sat Bhattacharya

Dr. Thomas Brennan

Harlem Children Society

Bronx Community College (Chemistry Department)

BCC Office of Collaborative Program (College Now)

City University of New York

National Science Foundation

Howard Hughes Medical Institute

Biological Science Curriculum Study

Pathways Bioinformatics & Biomolecular Center