Mar 11, 2008

Fight to HIV

Engineered cells against HIV

Engineered Immune cells can know be used to kill HIV infected cells before they become HIV virus producing factories. Researchers at Albert Einstein College of Medicine made a breakthrough in fight against HIV by transforming genetically engineered immune cells into potent weapons against the disease.

A subgroup of immune cells known as CD8 cytotoxic T lymphocytes or CTLs, recognize cells infected with HIV and kill them before they become HIV-producing factories. This CTL activity initially keeps the infection in check.

However, CTLs may not bind tightly enough to the infected cells or because HIV mutates so rapidly, the virus subdues the immune system, thus boosting the virus in the absence of drug therapy and resulting in AIDS.


The idea……

Certain of the CTLs of elite controllers may be genetically equipped to bind tightly to HIV-infected cells and destroy them and thereby suppress the infection indefinitely.

The idea was first to identify the elite controllers "super" CTLs and to isolate the genes that enable these cells to bind tightly to HIV-infected cells and kill them efficiently; then this gene
would be
transfer into CTLs that do not recognize HIV- infected cells and convert them into potent killers of those cells.

The breakthrough…….

CTLs T-cell receptor(TCR) has two chains- alpha and beta, that the researchers isolated the genes that code for each of the two "chains" from potent HIV-specific CTL.

The genes were combined and packaged inside a special type of virus, called a lentivirus. The lentiviruses the inserted these genes into chromosomes of naive CTLs obtained from a naïve donor's (not infected by HIV) blood and reprogrammed them into potent HIV-specific CTLs.

During the study, the researchers injected mice with both HIV infected human cells and with reprogrammed naïve CTLs into which the HIV recognizing T-cell receptor genes had been inserted using the lentiviral delivery system.

The findings revealed that after on week the infected cells had virtually been eliminated. Researchers found that these genetically reprogrammed CTLs have very strong activity in terms of killing HIV-infected cells in both test-tubes and an animal model. Researchers believe that the novel strategy could lead to and entirely new approach for combating AIDS and other viral diseases.


Mar 6, 2008



Upps Enzyme Antibody Abzymes confuses me….

The binding of an antibody to its antigen is similar in many ways to the binding of an enzyme to its substrate. In both cases the binding involves weak, noncovalent interactions and exhibits high specificity and often high affinity. What distinguishes an antibody-antigen interaction from an enzyme-substrate interaction is that the antibody does not alter the antigen, whereas the enzyme catalyzes a chemical change in its substrate. However, like enzymes, antibodies of appropriate specificity can stabilize the transition state of a bound substrate, thus reducing the activation energy for chemical modification of the substrate.


The similarities between antigen-antibody interactions and enzyme-substrate interactions raised the question of whether some antibodies could behave like enzymes and catalyze chemical reactions. To investigate this possibility, a hapten-carrier complex was synthesized in which the hapten structurally resembled the transition state of an ester undergoing hydrolysis. Spleen cells from mice immunized with this transition state analogue were fused with myeloma cells to generate monoclonal antihapten monoclonal antibodies. When these monoclonal antibodies were incubated with an ester substrate, some of them accelerated hydrolysis by about 1000-fold; that is, they acted like the enzyme that normally catalyzes the substrate’s hydrolysis. The catalytic activity of these antibodies was highly specific; that is, they hydrolyzed only esters whose transition-state structure closely resembled the transition state analogue used as a hapten in the immunizing conjugate. These catalytic antibodies have been called abzymes in reference to their dual role as antibody and enzyme.

What’s in Research??

A central goal of catalytic antibody research is the derivation of a battery of abzymes that cut peptide bonds at specific amino acid residues, much as restriction enzymes cut DNA at specific sites. Such abzymes would be invaluable tools in the structural and functional analysis of proteins. Additionally, it may be possible to generate abzymes with the ability to dissolve blood clots or to cleave viral glycoproteins at specific sites, thus blocking viral infectivity. Unfortunately, catalytic antibodies that cleave the peptide bonds of proteins have been exceedingly difficult to derive. Much of the research currently being pursued in this field is devoted to the solution of this important but difficult problem.