Sultana, Nishat Hadas, Yoav Sharkar, Mohammad Tofael Kabir Kaur, Keerat Magadum, Ajit Kurian, Ann Anu Hossain, Nadia Alburquerque, Bremy Ahmed, Sakib Chepurko, Elena
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Published in
Molecular therapy. Methods & clinical development
Modified mRNA (modRNA) is a gene-delivery platform for transiently introducing a single gene or several genes of interest to different cell types and tissues. modRNA is considered to be a safe vector for gene transfer, as it negligibly activates the innate immune system and does not compromise the genome integrity. The use of modRNA in basic and tr...
Gong, Ying Klein Wolterink, Roel G J Janssen, Ian Groot, Arjan J Bos, Gerard M J Germeraad, Wilfred T V
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Molecular therapy. Methods & clinical development
Adoptive natural killer (NK) cell therapy is attaining promising clinical outcomes in recent years, but improvements are needed. Genetic modification of NK cells with a tumor antigen-specific receptor on their surface coupled to intracellular signaling domains may lead to enhanced cytotoxicity against malignant cells. One of the most common approac...
Brendel, Christian Negre, Olivier Rothe, Michael Guda, Swaroopa Parsons, Geoff Harris, Chad McGuinness, Meaghan Abriss, Daniela Tsytsykova, Alla Klatt, Denise
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Published in
Molecular therapy. Methods & clinical development
In this work we provide preclinical data to support initiation of a first-in-human trial for sickle cell disease (SCD) using an approach that relies on reversal of the developmental fetal-to-adult hemoglobin switch. Erythroid-specific knockdown of BCL11A via a lentiviral-encoded microRNA-adapted short hairpin RNA (shRNAmiR) leads to reactivation of...
Madrakhimov, Sanjar Batirovich Yang, Jin Young Ahn, Dong Hyuck Han, Jung Woo Ha, Tae Ho Park, Tae Kwann
Published in
Molecular therapy. Methods & clinical development
The intravitreal (IVT) injection method is a choice when targeting the inner retina for gene therapy. However, the transduction efficiency of adeno-associated virus (AAV) vectors administered by the IVT route is usually low and may be affected by several factors. To improve the transduction efficiency, we developed a novel illuminated long-needle a...
Kuroda, Seiji Miyagawa, Yoshitaka Sato, Yuriko Yamamoto, Motoko Adachi, Kumi Kinoh, Hiromi Goins, William F Cohen, Justus B Glorioso, Joseph C Taniai, Nobuhiko
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Published in
Molecular therapy. Methods & clinical development
Non-toxic herpes simplex virus (HSV) vectors can be generated by functional deletion of all immediate-early (IE) genes, providing a benign vehicle with potential for gene therapy. However, deletion of multiple IE genes raises manufacturing concerns and thus limits clinical application of these vectors. To address this issue, we previously developed...
Ipseiz, Natacha Czubala, Magdalena A Bart, Valentina M T Davies, Luke C Jenkins, Robert H Brennan, Paul Taylor, Philip R
Published in
Molecular therapy. Methods & clinical development
Tissue-resident macrophages exhibit specialized phenotypes dependent on their in vivo physiological niche. Investigation of their function often relies upon complex whole mouse transgenic studies. While some appropriate lineage-associated promoters exist, there are no options for tissue-specific targeting of macrophages. We have developed full prot...
Patel, Shabnum Hanajiri, Ryo Grant, Melanie Saunders, Devin Van Pelt, Stacey Keller, Michael Hanley, Patrick J Simon, Gary Nixon, Douglas F Hardy, David
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Published in
Molecular therapy. Methods & clinical development
Although anti-retroviral therapy (ART) is successful in suppressing HIV-1 replication, HIV latently infected reservoirs are not eliminated, representing a major hurdle in efforts to eradicate the virus. Current strategies to eradicate HIV involve two steps: (1) the reactivation of latently infected cells with latency reversing agents (LRAs) to expo...
Prabhakar, Shilpa Cheah, Pike See Zhang, Xuan Zinter, Max Gianatasio, Maria Hudry, Eloise Bronson, Roderick T Kwiatkowski, David J Stemmer-Rachamimov, Anat Maguire, Casey A
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Published in
Molecular therapy. Methods & clinical development
Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome caused by mutations in TSC1 or TSC2, encoding hamartin and tuberin, respectively. These proteins act as a complex that inhibits mammalian target of rapamycin (mTOR)-mediated cell growth and proliferation. Loss of either protein leads to overgrowth in many organs, including subependymal...
Matsumura, Yuki Stiles, Katie M Reid, Jasmine Frenk, Esther Z Cronin, Samantha Pagovich, Odelya E Crystal, Ronald G
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Molecular therapy. Methods & clinical development
Aldehyde dehydrogenase 2 (ALDH2) deficiency causes "Asian flush syndrome," presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%-40% of East Asians and 8% of the world population. ALDH2 is the key enzyme in ethanol metabolism; with ethanol challenge, ...
Kondratova, Liudmyla Kondratov, Oleksandr Ragheb, Ragy Zolotukhin, Sergei
Published in
Molecular therapy. Methods & clinical development
Endotoxin is the most common contaminant found in protein samples. Even a small amount of endotoxin can induce strong allergic reaction and death of a host organism. Endotoxin is also often detected in recombinant adeno-associated virus (rAAV) stocks prepared in research laboratories using off-the-shelf reagents; purifying rAAV stocks from endotoxi...
