Article
Multidisciplinary Sciences
Martin Rodriguez, Brady Trevisan, Ritu M. Ramamurthy, Sunil K. George, Jonathan Diaz, Jordan Alexander, Diane Meares, Denise J. Schwahn, David R. Quilici, Jorge Figueroa, Michael Gautreaux, Andrew Farland, Anthony Atala, Christopher B. Doering, H. Trent Spencer, Christopher D. Porada, Graca Almeida-Porada
Summary: Hemophilia A is a common X-linked bleeding disorder with severe cases having very low FVIII levels leading to spontaneous and life-threatening bleeds. Researchers showed that prenatal transplantation of bioengineered human placental cells in sheep fetuses significantly increased FVIII levels for more than 3 years without triggering immune responses. This study demonstrates the feasibility and safety of treating hemophilia A before birth.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Asma Ghaemi, Masoume Vakili-Azghandi, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Mona Alibolandi
Summary: Gene therapy has the potential to prevent or treat various genetic or acquired diseases by regulating gene and protein expression. Effective delivery systems are needed to ensure successful gene therapy, and oral delivery approaches show promise in treating diseases such as inflammatory bowel disease and cancer. This review provides an update on the development of oral gene delivery techniques for gene therapy and vaccination purposes.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Multidisciplinary Sciences
Sajjad Afraz, Ivan Stevic, Davide Matino, Jianping Wen, Helen Atkinson, Anthony K. C. Chan, Gonzalo Hortelano
Summary: This study investigated the effects of co-administration of FVIII and IVIG on the development of inhibitors in hemophilia A mice. The results showed that mice receiving co-injections had significantly lower antibody titers compared to those receiving only FVIII injections. Interestingly, when IVIG co-administration was discontinued, antibody titers increased in some mice, while mice receiving continued co-administration had consistently low titers. These findings suggest that co-injection therapy with IVIG may be effective in managing hemophilia A patients at risk of inhibitor development.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Ritu M. Ramamurthy, Martin Rodriguez, Hannah C. Ainsworth, Jordan Shields, Diane Meares, Colin Bishop, Andrew Farland, Carl D. Langefeld, Anthony Atala, Christopher B. Doering, H. Trent Spencer, Christopher D. Porada, Graca Almeida-Porada
Summary: This study investigates the use of CRISPR/Cas9 for gene editing. The results demonstrate that while successful knockin of the RFP reporter gene was achieved, the insertion of the larger FVIII expression cassette was not successful. Additionally, the use of plasmids or introduction of the CRISPR/Cas9 machinery compromised the unique immune-inertness of PLCs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Brady Trevisan, Martin Rodriguez, Hailey Medder, Shannon Lankford, Rebecca Combs, John Owen, Anthony Atala, Christopher D. Porada, Graca Almeida-Porada
Summary: This study demonstrates the potential of using autologous bone marrow-derived mesenchymal stromal cells as cellular delivery vehicles for long-term expression of FVIII in the treatment of hemophilia A.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
John S. S. Butterfield, Xin Li, Sreevani Arisa, Kwang-Chul Kwon, Henry Daniell, Roland W. Herzog
Summary: Oral immunotherapies can suppress immune responses in an antigen-specific manner in the treatment of autoimmune diseases and allergies. Previous studies have shown that oral delivery of bioencapsulated coagulation factor antigens in transplastomic lettuce cells can prevent the formation of anti-drug antibodies in protein replacement therapy for hemophilia. This study demonstrates that this approach can also reduce antibody development against factor VIII in hemophilia A mice treated with gene transfer. Therefore, the concept of oral tolerance can be applied to prevent immune responses in gene therapy.
CELLULAR IMMUNOLOGY
(2023)
Article
Hematology
Weiqing Jing, Christina K. Baumgartner, Feng Xue, Jocelyn A. Schroeder, Qizhen Shi
Summary: In this study, we found that pre-existing inhibitors can lead to the loss of platelet-FVIII expression, and this loss is mediated by cytotoxic CD8 T cells. This finding is crucial for the treatment of hemophilia A patients with inhibitors.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Biotechnology & Applied Microbiology
Ilona Uzieliene, Ursule Kalvaityte, Eiva Bernotiene, Ali Mobasheri
Summary: Gene therapy has been explored as a potential treatment for osteoarthritis, with a focus on non-viral gene delivery technologies. While viral gene delivery has been more popular due to higher efficiency, efforts to enhance transfection efficiency of non-viral methods have shown promise for OA research and clinical applications. More research is needed to optimize transfection efficiency and duration of gene expression.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Chenfei Wang, Chaolan Pan, Haiyang Yong, Feifei Wang, Tao Bo, Yitong Zhao, Bin Ma, Wei He, Ming Li
Summary: Gene therapy holds great promise for treating a wide range of genetic diseases by delivering functional genes into targeted cells or tissues. However, the lack of safe and efficient gene delivery vehicles remains a major obstacle to its clinical implementation. This review comprehensively outlines the novel non-viral gene delivery vectors with potential applications in gene therapy.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Shuai Qu, Renfa Liu, Nisi Zhang, Yunxue Xu, Xiuli Yue, Zhifei Dai
Summary: This article reviews the recent advances in targeted non-viral nucleic acid delivery for gene therapy of atherosclerosis, including hepatocyte-targeted delivery and delivery to different cells within the plaques.
Review
Medicine, General & Internal
Alina-Andreea Zimta, Ionut Hotea, Melen Brinza, Cristina Blag, Sabina Iluta, Catalin Constantinescu, Atamyrat Bashimov, Elisabeth-Antonia Marchis-Hund, Alexandra Coudsy, Laetitia Muller-Mohnssen, Noemi Dirzu, Diana Gulei, Delia Dima, Margit Serban, Daniel Coriu, Ciprian Tomuleasa
Summary: Hemophilia type A is primarily inherited, but recent data suggests other molecular mechanisms may also contribute to the development or exacerbation of the disease. One area worth investigating further is the epigenetic silencing of the F8 gene.
FRONTIERS IN MEDICINE
(2021)
Article
Cell Biology
Ying Kai Chan, Sean K. Wang, Colin J. Chu, David A. Copland, Alexander J. Letizia, Helena Costa Verdera, Jessica J. Chiang, Meher Sethi, May K. Wang, William J. Neidermyer, Yingleong Chan, Elaine T. Lim, Amanda R. Graveline, Melinda Sanchez, Ryan F. Boyd, Thomas S. Vihtelic, Rolando Gian Carlo O. Inciong, Jared M. Slain, Priscilla J. Alphonse, Yunlu Xue, Lindsey R. Robinson-McCarthy, Jenny M. Tam, Maha H. Jabbar, Bhubanananda Sahu, Janelle F. Adeniran, Manish Muhuri, Phillip W. L. Tai, Jun Xie, Tyler B. Krause, Andyna Vernet, Matthew Pezone, Ru Xiao, Tina Liu, Wei Wang, Henry J. Kaplan, Guangping Gao, Andrew D. Dick, Federico Mingozzi, Maureen A. McCall, Constance L. Cepko, George M. Church
Summary: The study engineered AAV vectors by incorporating short DNA oligonucleotides to antagonize TLR9 activation, reducing innate immune responses and enhancing gene expression in clinically relevant animal models. The engineered vectors can avoid adverse reactions in some models, demonstrating a potential wider therapeutic window for AAV therapies.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Yi Yan, Xiao-Yu Liu, An Lu, Xiang-Yu Wang, Lin-Xia Jiang, Jian-Cheng Wang
Summary: RNA-based therapy is a promising strategy for disease treatment, and recent advances in non-viral delivery systems have shown potential in protecting RNA, facilitating cell internalization, and controlled release of therapeutics.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Medicine, Research & Experimental
Cynthia D. Anderson, Jennifer Ataam Arthur, Yuan Zhang, Nike Bharucha, Ioannis Karakikes, Ralph V. Shohet
Summary: CRISPR-Cas9-based genome editing technologies have the potential for clinical translation, but delivering nucleic acids into target cells in vivo is challenging. This study presents a new method using focused ultrasound targeted microbubble destruction to deliver CRISPR-Cas9 base editing vectors to the mouse liver. The results demonstrate successful base editing in mouse liver cells, but with lower specificity and more off-target base exchange in vivo.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Review
Immunology
Homa Boroumand, Fereshteh Badie, Samaneh Mazaheri, Zeynab Sadat Seyedi, Javid Sadri Nahand, Majid Nejati, Hossein Bannazadeh Baghi, Mohammad Abbasi-Kolli, Bita Badehnoosh, Maryam Ghandali, Michael R. Hamblin, Hamed Mirzaei
Summary: Viral infections can damage host cells and compromise the host immune system. Nanotechnology offers potential solutions for developing effective antiviral drugs with enhanced selectivity to protect healthy cells.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)