Secondcell Bio Publishes Biotechnology for Improved Drug Discovery Originating from The Rockefeller University

NEW YORK, Sept. 15, 2021 /PRNewswire/ -- Chromovert® Technology is a newly published disruptive technology for the genetic engineer's toolkit that originates from The Rockefeller University. The name comes from combining "chromosomes" and "convert."

Despite massive investments by the pharmaceutical industry, contemporary drug discovery has failed to deliver safe and effective drugs against the vast majority of drug targets identified to date. The inability to create laboratory cells that accurately mimic the biology of human disease for use as detectors during the discovery process is the fundamental handicap that subverts current efforts. Although billions of prospective drug compounds are tested against numerous disease genes, the lack of physiologically-relevant cell-based assays for reliable detection of promising lead compounds produces haphazard results. Chromovert is reported to enable creation of cells that accurately mimic human biology for improved results.

"Little more than a random and highly inefficient enterprise, drug discovery today is "garbage in, garbage out" enterprise. Chromovert increases reliability and efficiency of the resource-intensive process by allowing access to disease genes as they exist in the body," says Dr. Kambiz Shekdar, inventor.

Currently, the industry average failure rate for drug discovery programs in pharmaceutical companies is reported to be approximately 98%. Although this includes failures at all stages of the process, the high failure rate points to a dire need for any improvements in the efficiency of the process. One factor contributing to the high failure rate is the lack of cells that accurately mimic the biology of human disease in the laboratory dish. Indisputably, drug discovery research would benefit from cells that express drug targets in a form that mimics human disease with high fidelity for use in cell-based assays. Consequently, there is a great need for rapid and effective establishment of cell-based assays for more rapid discovery of new and improved drugs. Chromovert Technology is designed to fit the need. 

Compared to CRISPR which is especially well suited to deleting or disrupting target genes in treated cells, Chromovert enables the addition of one or more genes to cells. The technology was published in the Springer Nature journal Biotechnology Letters earlier this year  (https://link.springer.com/article/10.1007/s10529-021-03101-5). "Almost always, building something is harder than tearing it down. Similarly, knocking in genes poses a greater challenge than knocking them out," says Anna Nowogrodzki in The Scientist.

Previously, Chromovert was validated by its use in the discovery and development of a novel clinical stage non-addictive pain blocker fast-tracked by the FDA and natural flavors discovery. This work was performed by Chromocell Corporation, a biotechnology company spun out of The Rockefeller University based upon the technology. Dr. Shekdar and the late Nobel-Laureate Gunter Blobel served as the scientific co-founders of Chromocell. Dr. Blobel also served as the Chairman of the company's Scientific Advisory Board.

According to Dr. Blobel, "You can really test in a much more comprehensive way than you could previously, and therefore Chromovert will probably be important to eliminate side effects or to predict side effects and we can get better, more highly targeted drugs." "Interestingly, it was our work with human taste receptors the made us realize Chromovert can precisely mimic human biology," adds Dr. Shekdar. "Only data produced using Chromovert exactly mimicked human results."

Secondcell Bio is a new company formed to market optimized materials to operate the technology in partnership with, Gene Link, Inc., a leading custom oligo synthesis house with a license to manufacturer optimized and highly purified probes for use in living cells.

"In connection with the first scientific publication of Chromovert Technology earlier this year, Kambiz and I are making the oligos and other research materials needed to operate the method broadly available to the research community via our e-commerce platform at Gene Link," says Dr. Ali Javed, Gene Link Director of R&D.

Secondcell hopes researchers may use Chromovert to usher a new era of Drugomics™ by implementing improved drug discovery for targets identified in the last 20 years of Genomics.

Technical highlights for cell and genetic engineers:

Chromovert® Technology is ideally suited for researchers who aim to engineer cells or inherently stable cell lines comprising one or more added genes. Chromovert uses fluorogenic oligonucleotide signaling probes to detect desired genetic sequences in living cells coupled with flow cytometry to isolate positive cells. The probes may be directed to any gene of interest. Highly optimized protocols have been published for CHO and HEK 293 cell types.

Chromo-Tags™ obviate the need to create gene-specific probes. A family of 20 optimized mammalian expression vectors named pChromo-Plasmids™ is available from Secondcell Bio. The plasmids comprise novel synthetic DNA sequences subcloned downstream of Multiple Cloning Site (MCS) of Chromo-Plasmids for use to add 3´ untranslated detection tags to mRNA expression products termed Chromo-Tags™. Chromo-Tags function like epitope detection tags except they are expressed at the mRNA level only so that protein sequences remain unmodified.

Chromovert may be used to isolate thousands of high expressing clones. When coupled with automated robotic methods for miniaturized cell culture, functional testing over time may be used to identify inherently stable cell lines that can be maintained in continuous culture in the absence of any selective pressure without loss of expression. Also, cDNA expression libraries using Chromo-Tags may be used to create libraries of cell lines, or Cellbraries™.

Advantages of Chromovert for a broad variety of targets including heteromultimeric ion channel and native GPCR normally expressed in specialized cells such as neurons or epithelial cells have been reported. The Chromovert Advantage rests in its unique ability to scan hundreds of millions of cells to detect and isolate the exceedingly rare cells that provide the necessary host genetic background and cellular milieu for proper functional and viable expression of genes that are otherwise challenging to express in laboratory cells.

Chromovert is a broad-ranging platform cell engineering technology which may also be used for biologics production, production of cell therapy agents (e.g., recombination adeno-associated virus (rAAV)) and as a tool to engineer next generation allogenic CAR-T. Chromovert can also be used to increase the efficiency of cell therapy strategies to cure disease, including a novel cures for HIV-1 infection and sickle cell disease.

ABOUT CHROMOVERT TECHNOLOGY

Chromovert® Technology enables to creation of highly desired cell for improved drug discovery. The technology was invented by Dr. Kambiz Shekdar in the Nobel-Prize winning laboratory of the late Gunter Blobel, M.D., Ph.D., at The Rockefeller University. Materials and methods to operate Chromovert are available from Secondcell Bio at https://www.secondcellbio.com/.

Citation and Abstract of Chromovert® Technology Publication:

Shekdar, K., Langer, J., Venkatachalan, S. et al. Cell engineering method using fluorogenic oligonucleotide signaling probes and flow cytometry. Biotechnol Lett 43, 949–958 (2021). https://doi.org/10.1007/s10529-021-03101-5. https://link.springer.com/article/10.1007/s10529-021-03101-5

Objective: Chromovert® Technology is presented as a new cell engineering technology to detect and purify living cells based on gene expression.

Methods: The technology utilizes fluorogenic oligonucleotide signaling probes and flow cytometry to detect and isolate individual living cells expressing one or more transfected or endogenously-expressed genes.

Results: Results for production of cell lines expressing a diversity of ion channel and membrane proteins are presented, including heteromultimeric epithelial sodium channel (αβγ-ENaC), sodium voltage-gated ion channel 1.7 (NaV1.7-αβ1β2), four unique γ-aminobutyric acid A (GABA_A) receptor ion channel subunit combinations α1β3γ2s, α2β3γ2s, α3β3γ2s and α5β3γ2s, cystic fibrosis conductance regulator (CFTR), CFTR-Δ508 and two G-protein coupled receptors (GPCRs) without reliance on leader sequences and/or chaperones. In addition, three novel plasmid-encoded sequences used to introduce 3' untranslated RNA sequence tags in mRNA expression products and differentially-detectable fluorogenic probes directed to each are described. The tags and corresponding fluorogenic signaling probes streamline the process by enabling the multiplexed detection and isolation of cells expressing one or more genes without the need for gene-specific probes.

Conclusions: Chromovert Technology is provided as a research tool for use to enrich and isolate cells engineered to express one or more desired genes.

ABOUT SECONDCELL BIO, LLC

Secondcell Bio, LLC is a biotechnology company established to achieve previously inaccessible goals in cell and genetic engineering via dedicated research and commercialization partnerships. For more information, please visit https://www.secondcellbio.com/.

Secondcell, Secondcell Bio, Cellbrary, Cellbraries, Chromo-Plasmid, pChromo-Plasmid, Chromo-Tag, Drugomics, Drug Discovery at Scale, and the Secondcell Bio logo are trademarks of Secondcell Bio, LLC. Chromovert® Technology is a registered trademark of Chromocell Corporation.

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SOURCE Secondcell Bio, LLC