NIH Revises Guidelines For Human Gene Research Protocols

In order to streamline the review process for human gene transfer protocols, National Institutes of Health, US, revised its guidelines for controversial research involving recombinant or synthetic nucleic acid molecules. According to the Guide notice, the changes would impact three aspects: a) the selection of protocol criteria for in-depth review and public discussion by the NIH Recombinant DNA Advisory Committee (RAC); b)the process of reviewing human gene transfer registration and; c) streamlining the NIH submission requirements for approval of research work having ethical limitations. This step was taken by NIH to incorporate the changes suggested by the Institute of Medicine (IOM) in response to the original human gene transfer protocols, outlined by the NIH Office of Science Policy (OSP) in a Federal Register Notice issued on October 16, 2015. The final issue of the NIH Guidelines was published in the Federal Register on March 22, 2016.

Guidelines For Human Gene Research

The policy is expected to be enacted from April 27, 2016, which provides plenty of time to institutes and investigators to devise a plan of action for implementation of new procedures. The formulated protocol is expected to be reviewed by RAC in case of possession of scientific, societal or ethical concerns in any rDNA gene transfer research protocol, highlighted by the Director NIH Francis S. Collins.

Recombinant DNA molecule is a genetically engineered molecule, containing foreign DNA fragment inserted into a vector (carrier molecule) mostly plasmid or yeast, to create new genetic combinations or amplification of beneficial genetic trait artificially. The DNA combination formed in such a way is known as chimera, as it includes DNA from two diverse species. For example, in case of insulin production by bacteria, human insulin gene is inserted into a part of bacterial vector and the end product provides commercially available insulin which is then used by diabetics.

According to the new guidelines, the very first amendment regarding the selection criteria of a research protocol includes approval from the two major concerned government’s regulatory bodies: Institutional Biosafety Committee ‘IBC’ and Institutional Review Board ‘IRB’. Both of these regulatory bodies will then send the research protocol to NIH, which will forward the proposal to RAC for further action regarding the reviewing of potential controversial research.

It all started in 2005, when the NIH put a limit on research on human stem cells in addition to primate embryos. Finally in September 2015, the National Institutes of Health put a hold on research funding for chimeric human/nonhuman embryos until new funding guidelines were established due to ethical considerations. According to NIH, the research work for replication of human stem cells in animal embryos cannot be allowed at any cost. However, the researchers while backing up their research work said that the ban should be lifted as their work on chimeras would create new advancement in understanding early human development phases, and will improve the knowledge about devastating diseases to facilitate drug testing for safer and effective therapies.

The researchers added, “Currently, it is impossible to accurately recapitulate human development in vitro, and there is no ethical method to obtain post-implantation stage human fetal tissue for isolating tissue and organ stem cells for regenerative medicine.”

In September 2015 the NIH stated that they wanted to “evaluate the state of the science in this area”. That area being a mixture of human and animal cells, the agency issued a notice saying the Agency may consider a possible policy revision in this area.

In October 2015, the NIH granted a research award of up to $500,000 on an annual basis for five years to researchers to pursue innovative research in developmental biology; however, the application was on hold because NIH was reconsidering its rules for research on human stem cells incorporation in very early animal embryos. The innovative strategy can result in revolutionary production of tissues or organs for transplantation.

The NIH guidelines also suggest that at least one criterion mentioned in the report should be followed by the research protocol to be reviewed by RAC. According to the guidelines, any research protocol using risk causing agent like a new vector, genetic material, or delivery methodology associated with the threat of representing inhumane experience for the first time would be reviewed before approval. Secondly, a protocol relying on preclinical safety data obtained using a new preclinical model system of unknown and unconfirmed value would also be sent to RAC for review.

A vector, gene or the delivery method associated with unknown toxicities would also be reviewed by RAC, on the request of revision sent by the regulatory bodies. ‘NIH will review the request and notify the requestor of a decision within 10 working days’, as mentioned in the federal register report. Hence, the final verdict for the research protocol to be reviewed by the RAC would be in the hands of NIH.

The second main clause of the rDNA research guidelines was the selection process by which human gene transfer protocols are reviewed and registered with NIH. It was suggested that human gene transfer protocols which followed Section III–C of the NIH guidelines will continue the registration in the same way with minor amendments mentioned in detail in the federal register report, along with the streamlined protocol submission requirements.

Enzymes Involved In Recombinant DNA Technology

Special types of cleaving and linking enzymes are used in recombinant technology. The vector DNA in which foreign DNA is inserted has to be cleaved first to make room for welcoming new DNA. After the successful insertion of foreign DNA, both of the DNA fragments are joined together with the help of enzymes. Bacterial restriction endonucleases cleave DNA at more than a hundred distinct recognition sites, whereas DNA ligases are used for joining the DNA strand with the vector’s DNA strand. Once the rDNA molecule is formed, it can be introduced back into the host molecule in which desired characters are required, with the help of carrier molecules known as vectors. Recombinant DNA combinations are possible because DNA molecules from all organisms share the same chemical structure and differ only in the nucleotide sequence within that identical overall structure.

Advances In rDNA Technology

The number of recombinant proteins/DNA used for academic research and therapeutic applications has increased dramatically since 1990s after successful cloning of Dolly the sheep.

Recombinant DNA technology has applications in the field of medicine, agriculture, animal husbandry, and the GMOs. Treatments for cancer, production of transgenic insect-resistant crops, as well as advances in the production of growth hormones along with transgenic animals, can be credited to the success of recombinant DNA technology.

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