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Drolet, Daniel; Nelson, J. Arly; Tucker, Christopher E.; Zack, Philip M.; Nixon, Kerry; Bolin, Richard; Judkins, Mark B.; Farmer, James A.; Wolf, Julie; Gill, Stanley C.; Bendele, Raymond A.

doi:10.1023/a:1007657109012

Cited by 173 publications

(48 citation statements)

References 21 publications

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“…Four anti-VEGF pharmacologic agents are now commercially available and being in use in trials for treatment of diabetic macular edema (DME) and PDR. Pegaptanib ( Macugen , OSI/Eyetech, Melville, NY, USA) is a modified 28-base RNA aptamer, which binds to VEGF 165 isoform inhibiting its vascular permeability effects [180]. Pegaptanib was tested in vitro which showed significance inhibition of VEGF induced vascular permeability [181].…”

Section: Treatment Of Retinal Neovascularizationmentioning

confidence: 99%

Targeting neovascularization in ischemic retinopathy: recent advances

Al‐Shabrawey

El‐Sherbiny

Nussbaum

et al. 2013

Expert Review of Ophthalmology

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Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities.

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Section: Treatment Of Retinal Neovascularizationmentioning

confidence: 99%

Targeting neovascularization in ischemic retinopathy: recent advances

Al‐Shabrawey

El‐Sherbiny

Nussbaum

et al. 2013

Expert Review of Ophthalmology

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“…The observation that the VEGF aptamer remains active and can be recovered from the vitreous humour of rhesus monkeys 28 days after injection [53] is encouraging with regard to prospects for long-term ocular retention of the compound. Because most existing drugs are protein antagonists, the ultimate success of aptamers as therapeutic agents will probably depend on how well they compete with other classes of therapeutic compounds.…”

Section: Pegaptanib (Macugen): Breakthrough In the Therapeutic Applicmentioning

confidence: 98%

DNA and RNA Aptamers: From Tools for Basic Research Towards Therapeutic Applications

Ulrich

Trujillo²,

Nery³

et al. 2006

CCHTS

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The systematic evolution of ligands by exponential enrichment (SELEX) is a combinatorial oligonucleotide library-based in vitro selection approach in which DNA or RNA molecules are selected by their ability to bind their targets with high affinity and specificity, comparable to those of antibodies. Nucleic acids with high affinity for their targets have been selected against a wide variety of compounds, from small molecules, such as ATP, to membrane proteins and even whole organisms. Recently, the use of the SELEX technique was extended to isolate oligonucleotide ligands, also known as aptamers, for a wide range of proteins of importance for therapy and diagnostics, such as growth factors and cell surface antigens. The number of aptamers generated as inhibitors of various target proteins has increased following automatization of the SELEX process. Their diagnostic and therapeutic efficacy can be enhanced by introducing chemical modifications into the oligonucleotides to provide resistance against enzymatic degradation in body fluids. Several aptamers are currently being tested in preclinical and clinical trials, and aptamers are in the process of becoming a new class of therapeutic agents. Recently, the anti-VEGF aptamer pegaptanib received FDA approval for treatment of human ocular vascular disease.

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“…The advantages include high specificity and binding affinity for the target antigen, minimal immunogenicity, and easy modification (Drolet et al, 2000; Torchilin, 2005). Aptamers are stable over wide temperature and pH ranges, and they are stable in organic solvents (Nimjee et al, 2005; Wilson and Szostak, 1998).…”

Section: Targeting Moietiesmentioning

confidence: 99%

Bioengineering Strategies for Designing Targeted Cancer Therapies

Alexander-Bryant

Berg-Foels

Wen

2013

Advances in Cancer Research

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The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes.

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Abstract: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.

Cited by 173 publications

References 21 publications

Targeting neovascularization in ischemic retinopathy: recent advances

Targeting neovascularization in ischemic retinopathy: recent advances

DNA and RNA Aptamers: From Tools for Basic Research Towards Therapeutic Applications

Bioengineering Strategies for Designing Targeted Cancer Therapies

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