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1.
Acta Pharmaceutica Sinica ; (12): 287-295, 2022.
Article in Chinese | WPRIM | ID: wpr-922905

ABSTRACT

Diabetic retinopathy (DR), one of the common complications of diabetes, is the main cause of blindness. Due to the limitations of the existing clinical treatment methods, it is urgent to develop new targets or/and new therapeutic drugs. This review summarizes the clinical trials of anti-DR drugs in recent years, and we note that gene therapy is a potential direction for DR treatment development. Due to the characteristics of ocular structure, including small size, a relatively independent organ, immune privilege and the opportunity for local administration, gene therapy could well be advantageous in the treatment of DR. Furthermore, the long-term therapeutic effects of gene therapy also improve compliance by DR patients. All these indicate that gene therapy is likely a future direction for development of DR therapies.

2.
Rev. bras. oftalmol ; 80(2): 100-106, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1280105

ABSTRACT

ABSTRACT Objective: A scientometric analysis produced in ophthalmic genetics and gene therapy research is lacking. The purpose of this study is to present a holistic analysis of ophthalmic genetics literature. Methods: The data used in this study were obtained from the Web of Science (WoS) Core Collection. All published documents between 1975-2019 were included. The data exported from WoS enabled the extensive details of ophthalmic genetics related literature including countries, institutions, authors, citations and keywords. Scientometric network maps of keywords and also country and institution co-authorships were created with free software. Global contributions of the countries to the ophthalmic genetics literature were shown by a graphic. Results: The search query revealed a total of 2322 documents. Most of the documents were original articles (75.75%). USA was the leading country by producing 45.39% of all documents in ophthalmic genetics research followed by UK, Germany, China and France. Pennsylvania University was the most contributing institution in the literature (5.25%) followed by University College London and Moorfields Eye Hospital. The average citations per item was 29.4. The most used keywords over a 40-year period were 'family', 'cell', 'photoreceptor' and 'expression'. Conclusions: USA and UK dominated the ophthalmic genetics research. A substantial increase in the number of published documents in this field were observed after 2010.


RESUMO Objetivo: A literatura carece de análise cienciométrica produzida em genética oftálmica e de pesquisa em terapia genética. O objetivo deste estudo é apresentar uma análise holística da literatura genética oftálmica. Métodos: Os dados utilizados neste estudo foram obtidos na base de dados Web of Science (WoS) Core Collection. Todos os documentos publicados entre 1975 e 2019 foram incluídos na análise. Os dados exportados da WoS viabilizaram acesso a amplos detalhes da literatura relacionada à genética oftálmica, incluindo países, instituições, autores, citações e palavras-chave. Mapas de rede cienciométrica foram criados por meio de software gratuito, com base em palavras-chave e em coautorias de países e instituições. As contribuições globais dos países para a literatura sobre genética oftálmica foram apresentadas em gráfico. Resultados: a busca por pesquisas revelou um total de 2.322 documentos cuja maioria eram artigos originais (75,75%). Os EUA foram o país que mais produziu artigos sobre o tema, com 45,39% de todos os documentos em pesquisa genética oftálmica; ele foi seguido pelo Reino Unido, Alemanha, China e França. A Universidade da Pensilvânia foi a instituição que mais contribuiu para a literatura (5,25%), e foi seguida pela University College London e pelo Moorfields Eye Hospital. A média de citações por item foi de 29,4. As palavras-chave mais usadas em um período de 40 anos foram 'família', 'célula', 'fotorreceptor' e 'expressão'. Conclusões: Os EUA e o Reino Unido dominaram a pesquisa em genética oftálmica. Após 2010, observou-se um aumento substancial no número de documentos publicados nessa área.


Subject(s)
Humans , Genetic Therapy , Bibliometrics , Eye Diseases, Hereditary , Eye Diseases/genetics , Eye Diseases/therapy , Ophthalmology/trends , Periodicals as Topic/trends , Periodicals as Topic/statistics & numerical data , Publications , Publishing/statistics & numerical data , Databases, Factual , Genomics/trends , Genetic Research
3.
J. pediatr. (Rio J.) ; 97(supl.1): 39-48, Mar.-Apr. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1250227

ABSTRACT

Abstract Objectives: Inborn Errors of Immunity (IEI), also known as primary immunodeficiencies, correspond to a heterogeneous group of congenital diseases that primarily affect immune response components. The main clinical manifestations comprise increased susceptibility to infections, autoimmunity, inflammation, allergies and malignancies. The aim of this article is to review the literature on combined immunodeficiencies (CIDs) focusing on the diagnosis and treatment and the particularities of the clinical management of these patients. Source of data: Critical integrative review, aimed to present articles related to primary immunodeficiencies combined with a searchin the PubMed and SciELO databases, with evaluation of publications from the last twenty years that were essential for the construction of knowledge on this group of diseases. Summary of data: We highlight the main characteristics of CIDs, dividing them according to their pathophysiological mechanisms, such as defects in the development of T cells, TCR signaling, co-stimulatory pathways, cytokine signaling, adhesion, migration and organization of the cytoskeleton, apoptosis pathways, DNA replication and repair and metabolic pathways. In CIDs, clinical manifestations vary widely, from sinopulmonary bacterial infections and diarrhea to opportunistic infections, caused by mycobacteria and fungi. Neonatal screening makes it possible to suspect these diseases before clinical manifestations appear. Conclusions: The CIDs or IEI constitute a complex group of genetic diseases with T-cell involvement. Neonatal screening for these diseases has improved the prognosis of these patients, especially in severe ones, known as SCIDs.

4.
J. pediatr. (Rio J.) ; 97(supl.1): 17-23, Mar.-Apr. 2021. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1250229

ABSTRACT

Abstract Objectives: To provide an overview of drug treatment, transplantation, and gene therapy for patients with primary immunodeficiencies. Source of data: Non-systematic review of the literature in the English language carried out at PubMed. Synthesis of data: The treatment of patients with primary immunodeficiencies aims to control their disease, especially the treatment and prevention of infections through antibiotic prophylaxis and/or immunoglobulin replacement therapy. In several diseases, it is possible to use specific medications for the affected pathway with control of the condition, especially in autoimmune or autoinflammatory processes associated with inborn immunity errors. In some diseases, treatment can be curative through hematopoietic stem cell transplantation (HSCT); more recently, gene therapy has opened new horizons through new technologies. Conclusions: Immunoglobulin replacement therapy remains the main therapeutic tool. Precision medicine with specific drugs for altered immune pathways is already a reality for several immune defects. Advances in the management of HSCT and gene therapy have expanded the capacity for curative treatments in patients with primary immunodeficiencies.

5.
Rev. Hosp. Ital. B. Aires (2004) ; 41(1): 37-42, mar. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1178964

ABSTRACT

El término CRISPR, por su acrónimo en inglés refiere a Clustered Regularly Interspaced Short Palindromic Repeats, es decir, repeticiones palindrómicas cortas, agrupadas y regularmente esparcidas, por sus características en el genoma, pertenece naturalmente al sistema de defensa de bacterias y arqueas. Este ha sido adaptado biotecnológicamente para la edición del ADN de células eucariotas, incluso de células humanas. El sistema CRISPR-Cas para editar genes consta, en forma generalizada, de dos componentes: una proteína nucleasa (Cas) y un ARN guía (sgRNA). La simplicidad del complejo lo hace una herramienta molecular reprogramable capaz de ser dirigida y de editar cualquier sitio en un genoma conocido. Su principal foco son las terapias para enfermedades hereditarias monogénicas y para el cáncer. Sin embargo, además de editor de genes, la tecnología CRISPR se utiliza para edición epigenética, regulación de la expresión génica y método de diagnóstico molecular. Este artículo tiene por objetivo presentar una revisión de las aplicaciones de la herramienta molecular CRISPR-Cas, particularmente en el campo biomédico, posibles tratamientos y diagnósticos, y los avances en investigación clínica, utilizando terapia génica con CRISPR/Cas más relevantes hasta la fecha. (AU)


CRISPR are Clustered Regularly Interspaced Short Palindromic Repeats, which naturally belong to the defense system of bacteria and archaea. It has been biotechnologically adapted for editing the DNA of eukaryotic cells, including human cells. The CRISPR-Cas system for editing genes generally consists of two components, a nuclease protein (Cas) and a guide RNA (sgRNA). The simplicity of the complex makes it a reprogrammable molecular tool capable of being targeted and editing any site in a known genome. Its main focus is therapies for monogenic inherited diseases and cancer. However, in addition to gene editor, CRISPR technology is used for epigenetic editing, regulation of gene expression, and molecular diagnostic methods. This article aims to present a review of the applications of the CRISPR-Cas molecular tool, particularly in the biomedical field, possible treatments and diagnoses, and the advances in clinical research, using the most relevant CRISPR-Cas gene therapy to date. (AU)


Subject(s)
Humans , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , CRISPR-Cas Systems/genetics , Biotechnology , Genetic Therapy/methods , Gene Expression , Genome, Human/genetics , Gene Expression Regulation , Epigenomics/trends , CRISPR-Associated Proteins/genetics , CRISPR-Associated Proteins/therapeutic use , Genetic Diseases, Inborn/therapy , Neoplasms/therapy
6.
Rev. invest. clín ; 73(1): 39-51, Jan.-Feb. 2021. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1289743

ABSTRACT

ABSTRACT Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have long-term effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis. (REV INVEST CLIN. 2021;73(1):39-51)

7.
International Eye Science ; (12): 1205-1208, 2021.
Article in Chinese | WPRIM | ID: wpr-877385

ABSTRACT

@#Retinitis pigmentosa(RP)is a hereditary retinal disease characterized by degeneration of retina rods and cones photoreceptor cells and degeneration of retinal pigment epithelial cells. The age of onset and progression of RP are genetically related and influenced by the environment. Gene therapy uses vectors in delivering therapeutic genes to genetically modify target cells, so as to correct or replace the disease-causing RP genes. This article introduces the research progress of vectors in RP gene therapy, and review the efficacy and safety of gene therapy on five common genotypes(RHO, PDE6B, MERTK, RLBP1, RPGR).

8.
Article in Chinese | WPRIM | ID: wpr-912422

ABSTRACT

Retinitis pigmentosa is a hereditary disease which is characterized by damage in retinal photoreceptor cells and retinal pigment epithelium. Its main clinical features include low vision with night blindness, progressive visual field defects, and abnormal electroretinograms. The development of gene sequencing, the diagnosis and treatment methods of retinitis pigmentosa update year by year, including gene therapy, stem cell therapy, optogenetic therapy, etc. However, there is still a big gap in these treatments from laboratory technology into effective clinical treatment drugs. Some problems which include immune response, potential mutagenesis and tumorigenesis of the inserted region, genetic toxicity, quality and stability of gene technology and stem cell technology, mass production and promotion of clinical grade drugs, and optimization of the effectiveness of drugs and surgery, etc, remain to be solved by researchers.

9.
Article in Chinese | WPRIM | ID: wpr-912421

ABSTRACT

X-linked juvenile retinoschisis (XLRS) is a rare X-linked inherited retinal disorder, mainly affects bilateral retina. Patients often present with visual deterioration accompanied by a spoke-wheel pattern in the macula due to splitting of inner retinal layers and a disproportionate decline in the b-wave relative to a-wave of electroretinogram. The current therapy is mainly directed toward treatment of complications with no effective clinical management yet. In recent years, with the deepening understanding of XLRS, adeno-associated virus(AAV)-mediated gene therapy has become a potential new approach for the treatment. Two clinical trials on XLRS gene therapy are currently underway. These two clinical trials assess the ocular safety and tolerability of recombinant AAV- RS1 vector and explore its safe dose in XLRS patients. However, the recovery of retinal structure and function in XLRS patients is unsatisfactory. Following the in-depth research and progress of clinical trials, it is expected that more accurate and effective treatments for XLRS patients will be provided in the future.

10.
Article in Chinese | WPRIM | ID: wpr-912388

ABSTRACT

Fundus disease is a kind of common ophthalmic disease with high blindness rate and great harm. Although great breakthroughs have been made in medical treatment, laser photocoagulation, radiotherapy and gene therapy of fundus disease, with the further understanding of the essence of fundus disease, there are higher requirements for the treatment of fundus disease. To strengthen scientific research on the etiology, pathological mechanism and clinical treatment of fundus diseases, to control the quality of research, to develop reasonable treatment plans and explore new treatment methods under the guidance of evidence-based medicine theory, to further improve the level of medical treatment and benefit patients with fundus diseases will still be a formidable challenge in the future.

11.
Article in Chinese | WPRIM | ID: wpr-912384

ABSTRACT

Retinitis pigmentosa (RP) is an inherited retinal disease characterized by degeneration of retinal pigment epithelial cells. Precision medicine is a new medical model that applies modern genetic technology, combining living environment, clinical data of patients, molecular imaging technology and bio-information technology to achieve accurate diagnosis and treatment, and establish personalized disease prevention and treatment model. At present, precise diagnosis of RP is mainly based on next-generation sequencing technology and preimplantation genetic diagnosis, while precise therapy is mainly reflected in gene therapy, stem cell transplantation and gene-stem cell therapy. Although the current research on precision medicine for RP has achieved remarkable results, there are still many problems in the application process that is needed close attention. For instance, the current gene therapy cannot completely treat dominant or advanced genetic diseases, the safety of gene editing technology has not been solved, the cells after stem cell transplantation cannot be effectively integrated with the host, gene sequencing has not been fully popularized, and the big data information platform is imperfect. It is believed that with the in-depth research of gene sequencing technology, regenerative medicine and the successful development of clinical trials, the precision medicine for RP will be gradually improved and is expected to be applied to improve the vision of patients with RP in the future.

12.
Article in Chinese | WPRIM | ID: wpr-912374

ABSTRACT

Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK- 001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.

13.
Chinese Journal of Neurology ; (12): 1103-1108, 2021.
Article in Chinese | WPRIM | ID: wpr-911844

ABSTRACT

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single gene hereditary cerebral small vessel disease in adults. With the development of gene sequencing technology and imaging, the disease is more and more recognized by people. In this paper, according to the research progress in recent years, the mutation types of NOTCH3 gene in CADASIL patients, the hot spot regions and sites of mutation in different populations, and the relationship between genotype and phenotype were summarized from the perspective of genetics. The future gene therapy of the disease was prospected.

14.
Article in Chinese | WPRIM | ID: wpr-911381

ABSTRACT

Objective:To investigate the role and mechanism of long non-coding RNA GAS5 in the targeted regulation of miR-29, miR-96, and miR-208 in promoting insulin secretion of pancreatic β-cells.Methods:Q-PCR was used to detect the expression of miR-29, miR-96, and miR-208 in sera of 122 healthy subjects and 88 type 2 diabetic patients; and so of long non-coding RNA GAS5 and miR-208 in the rat islet cell tumor strain ins-1832/13. Effects of silencing and overexpressing GAS5 on insulin secretion of islet β-cells by lentiviral vector construction were observed. Bioinformatics was used to predict that GAS5 had complementary binding sites with miR-29, miR-96, and miR-208, which was further verified by luciferase reporting system. GAS5 siRNA was co-transfected with miR-29, miR-96, and miR-208 inhibitors, and the effect of GAS5 on insulin receptor (INSR), insulin receptor substrate (irs-1) and PI3K levels was detected by the above method, so as to reveal the effect of GAS5 on insulin secretion in islet cells.Results:The expression of GAS5 in serum of T2DM patients was lower than that of healthy control group ( t=4.632, P<0.01), and expression of miR-29, miR-96, and miR-208 were higher than those of healthy control group ( t were 7.832, 9.164, and 12.359, all P<0.01). GAS5 level was negatively correlated with miR-29, miR-96, and miR-208 ( r were -0.50, -0.47, and -0.70, respectively). GAS5 expression was significantly decreased in serum of type 2 diabetic patients compared with that of in healthy subjects. Overexpression of GAS5 by lentivirus resulted in increased glucose-stimulated insulin secretion and increased insulin concentration compared to negative control. In contrast, knockdown of GAS5 led to significant reduction of glucose-stimulated insulin secretion and insulin concentration. GAS5 levels were negatively correlated with miR-29, miR-96, and miR-208 in serum samples of type-2 diabetes patients. GAS5 can negatively regulate the expression of miR-96, miR-29, and miR-208. By bioinformatics tools, we screened miR-29, miR-96 and miR-208 as targets of GAS5, and their interaction was validated with dual luciferase reporter gene assay. shGAS5 significantly decreased the expressions of INSR, IRS-1 and PI3K( P were 0.022, 0.038, and 0.009), while overexpressed GAS5 significantly upregulated the expressions of INSR, IRS-1 and PI3K at both mRNA and protein levels( P were 0.024, 0.045, and 0.016). Conclusion:GAS5 could stimulate insulin secretion of islet cell through its inhibitry regulationor of expressions of miR-29, miR-96, and miR-208, therely up-regulating INSR, IRS-1, and PI3K that may be the potential targets of these miRNAs, and stimulate insulin secretion of islet cells.

15.
Article in Chinese | WPRIM | ID: wpr-908582

ABSTRACT

Neovascular macular degeneration (nAMD) is one of the main eye diseases causing blindness in the elderly population.Early detection and early treatment are particularly important.At present, the treatment of nAMD is mainly symptomatic, including anti-vascular endothelial growth factor (VEGF) and laser treatment etc., which can not solve the problem of persistent disease activity of nAMD.Repeated treatment increases the economic burden of patients, and also the incidence of complications, such as increased intraocular pressure and inflammatory reaction.In recent years, the extensive application of gene therapy has brought more possibilities for the treatment of nAMD.It takes virus as the vector, combines the cDNA of target genes with the vector, and realizes the expression of target genes in the host cell by making use of the virus infecting host cells.Based on the successful animal experiments, phase Ⅰ and phase Ⅱ clinical trials with pigment epithelium derived factor, RNA interference, soluble VEGF receptor 1, endostatin and angiostatin, anti-VEGF Fab, soluble CD59, aflibercept, complement factor I, etc.as targets have been conducted at home and abroad.Certain achievements have been made, but some problems are also exposed.In this paper, the mechanism, research progress of clinical trials and existing problems of gene therapy for nAMD were reviewed, and the prospect of gene therapy in the future was proposed.

16.
Article in Chinese | WPRIM | ID: wpr-908580

ABSTRACT

Inherited retinal degeneration (IRD), a group of diseases often causing irreversible blindness, with multiple pathogenesis, still lacks effective treatments currently.Development of effective therapeutics is a primary research goal.Despite rapid advances in gene therapy during the past decades, the most challenging aspect of gene therapy in clinical applications for IRD is to deliver the curative molecules to achieve optimal expression levels in target cells safely.Apart from high gene transfection efficiency, there are still many limitations, such as immunogenicity, biosafety issue, etc.in the application of viral vectors, which drive the development of gene therapy based on non-viral vectors.As one of the hot research topics in non-viral vectors, encouraging progress has been made in DNA nanoparticles for IRD treatment.The polymer/DNA complex nanoparticle is compacted and encapsulated DNA via peptides, lipids, or polysaccharides.Besides, the non-viral delivery system shows cost, preparation, packaging capacity, and safety advantages, providing a promising non-viral platform for safe and effective treatment of IRD, such as retinitis pigmentosa, Stargardt disease, X-linked juvenile retinoschisis, Leber congenital amaurosis, and so on.In this article, advances in transfection efficiency, targeting ability and safety of non-viral gene therapy and its application in IRD were reviewed.

17.
Article in Chinese | WPRIM | ID: wpr-908578

ABSTRACT

Objective:To evaluate the safety and clinical effect of gene therapy for Leber hereditary optic neuropathy (LHON).Methods:A multi-center prospective non-randomized controlled trial was conducted.Eighty eyes of 40 LHON patients with mitochondrial DNA 11778 mutation were enrolled in Taihe Hospital from December 2017 to February 2018.Intravitreal injection of recombinant adeno associated virus 2-NADH dehydrogenase 4 (rAAV2- ND4) was carried out in the unilateral eye with worse visual acuity or the right eye (if the visual acuity of both eyes was equal) of each subject as the treated group and the fellow eyes as the untreated group.The best corrected visual acuity (BCVA) was detected using a standard logarithmic chart and intraocular pressure (IOP) was measured with a non-contact tonometer before treatment and 1, 3, 6, 12 months after treatment.The manifestations of the ocular anterior segment and fundus were examined by slit lamp microscopy and color photography.The changes of visual acuity and IOP before and after gene therapy were compared, and complications were evaluated between the treated group and the untreated group.The effective rate defined as visual acuity improved ≥0.3 LogMAR at the end of follow-up was assessed.This study adhered to the Declaration of Helsinki and the study protocol was approved by an Ethics Committee of Taihe Hospital (No.201807). Written informed consent was obtained from each subject prior to any medical examination and treatment. Results:The visual acuity improved 6 eyes in the treated group and 4 eyes in the untreated group, and 13 patients showed bilateral improvement.The visual acuity improvement ≥0.3 LogMAR in 23 patients with the effective rate 57.5%.The BCVA was (1.51±0.62) LogMAR and (1.62±0.58) LogMAR at the end of following-up in the untreated group and treated group, respectively, which were significantly higher than (1.75±0.46) LogMAR and (1.83±0.47) LogMAR before treatment (both at P<0.01), and no significant difference was found in BCVA between the two groups ( Fgroup=0.084, P=0.772). There was no significant difference in IOP between the two groups before and after treatment ( Fgroup=0.557, P=0.575; Ftime=2.314, P=0.106). No serious complications were found in all subjects during following-up. Conclusions:rAAV2- ND4 gene therapy is safe and effective for LHON, and binocular vision can be improved by monocular intravitreal injection of rAAV2- ND4 gene.

18.
Article in Chinese | WPRIM | ID: wpr-908569

ABSTRACT

Most inherited retinal diseases (IRDs) severely impair vision and lack effective treatments.With the approval of Luxturna, the world's first gene therapy drug for IRDs in 2017 by the U. S.FDA, gene therapy has brought new hope for the treatment of the disease.With an early onset and a relatively small number of patients, the understanding of the natural course of IRDs is limited in the past.The research on gene therapy of IRDs is mainly based on the in-depth understanding of the pathogenesis and natural course of disease, and the selection of the optimal treatment window for the implementation of gene therapy is the premise of successful treatment.At the same time, the main vector for gene therapy is recombinant virus vector, and its tissue-immunogenicity, tumorigenicity, safety of its integration with host cells and effectiveness determine the outcome of therapy, so the evaluation technology of IRDs gene therapy needs to be established.Gene therapy for ophthalmic diseases also involves the consideration of laws and regulations, ethics, product process, races and regional environment, disease progression, gene mutation types, patient benefit and risk ratio, and other factors.Therefore, it is of great significance to take full account of the differences in IRDs population, especially the particularity of children patients, and actively carry out the study on the natural course of IRDs in China for the scientific and normative development of clinical trials of gene therapy, the effective establishment of endpoint and outcome indicators for clinical studies of gene therapy, and the compliance with international norms of ethics.

19.
Acta Pharmaceutica Sinica ; (12): 3451-3459, 2021.
Article in Chinese | WPRIM | ID: wpr-906823

ABSTRACT

Poly (β-amino ester)s (PβAEs) contain tertiary amine backbones and biodegradable ester bonds, making them highly biocompatible and pH-responsive. Meanwhile, originated from combinatorial libraries, PβAEs are simple to synthesize, easy to obtain raw materials and can be easily adapted to meet the different performance needs of gene carriers by adjusting the monomer type, monomer ratio and reaction time. Therefore, PβAEs are promising material for non-viral gene carriers. This paper provides a comprehensive overview of the properties and synthesis of PβAEs gene carriers and summarizes the progress of research on the gene delivery of each type of PβAEs.

20.
Acta Pharmaceutica Sinica ; (12): 2335-2345, 2021.
Article in Chinese | WPRIM | ID: wpr-886961

ABSTRACT

Oligonucleotides have attracted the widespread attention in disease diagnosis and gene therapy. At present, the nucleic acid drugs are at the forefront of biomedical and pharmaceutical research. The bioanalysis of therapeutic oligonucleotides has been slow, however, due to the requirements for pharmacokinetic/toxicokinetic and pharmacodynamic studies in pharmaceutical development. Conventionally, the hybridization-enzyme linked immunosorbent assay (hybridization-ELISA) is widely used in the bioanalysis of therapeutic oligonucleotides. Recentlly, many technologies such as real-time quantitative PCR (qPCR) and high performance liquid chromatography (HPLC)-based technologies have also showed a broad application prospects in the bioanalysis of therapeutic oligonucleotides. However, each technology has its own advantages and limitations. This review summarizes the currently used techniques in the bioanalysis of oligonucleotide therapeutics and reviews the challenges of regulated bioanalysis.

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