近年来，基因治疗愈来愈火热，基因治疗药物陆续被批准上市，为多种疾病的治疗带来了新的解决方案。

所谓的基因治疗（gene therapy），从广义上来说，是将某种遗传物质(DNA/RNA)转移到患者体内并发挥作用，从而达到治疗疾病的目的。从狭义上来说或，是将外源的正常基因通过基因工程技术转移到病人的适当的靶细胞内，通过外源基因的产物来治疗由于纠正/补偿因基因缺陷/异常所引起的疾病，从而达到治疗的目的。

因此，基因治疗为囊性纤维化、HIV感染和某些肿瘤等多种疾病提供了一系列潜在的治疗方法。基因治疗的有效性受到适当载体的选择、对新合成蛋白质的免疫反应以及转移基因的持久性的影响。所以，对该基因的递送选择需要谨慎选择。最佳的递送系统应提高转染效率，同时将副作用降至最低。

ALZET渗透泵在基因治疗研究的成功中发挥了重要作用，允许将基因载体直接局部递送到靶区，同时消除了通常与全身给药相关的大多数副作用。此外，随着时间的推移，保持缓慢、连续的载体输注可最大限度地减少局部组织损伤。此外，缓慢的输注增加了病毒和细胞之间的接触时间，从而提高了转导效率。

ALZET渗透泵已经在基因治疗研究中有着广泛的应用，特别是在以下几个方面有着广泛的文献报道：

（1）Antisense Oligonucleotides

文献一：A. Saoudi, et al. Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models. Cells 2023;12(6):

Agents: Oligonucleotides, antisense Vehicle: Not Stated;Route: CSF/CNS (intracerebroventricular);Species: Mice;Strain: hDMD;mdx52;Pump: 1002;Duration: 2 weeks;

ALZET Comments: Dose (~700 nmol);animal info: 6–8-week-old mdx52 and WT mice;comparison of bolus injection vs mp;neurodegenerative (neurological disorder);brain tissue distribution

文献二：I. Michailidou, et al. The systemic inhibition of the terminal complement system reduces neuroinflammation but does not improve motor function in mouse models of CMT1A with overexpressed PMP22. Current Research in Neurobiology 2023;4(100077

Agents: Oligonucleotide, antisense Vehicle: PBS; Route: SC; Species: Mice; Strain: C3-PMP22 (C22-PMP22 x C57BL/6); Pump: 1007D; Duration: Not Stated;

ALZET Comments: Dose (5 mg/kg); Controls received mp w/ vehicle; animal info: C57Bl/6 mice; C6 LNA oligonucleotide targets mRNA of C6; neurodegenerative (Charcot-Marie-Tooth disease)

（2）Nanoparticles

文献一：J. S. Rechberger, et al. Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery. Neurosurgical Focus 2020;48(1):E2

Agents: FITC-Dextran Vehicle: Saline; Route: CSF/CNS; Species: Rat; Pump: 2001D; 2ML1; Duration: 24 hours; 5 days;

ALZET Comments: Animal info (Female Sprague-Dawley rats (mean age 6 weeks, mean weight 140 g));

文献二：S. Fujiwara, et al. Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury. In Vivo 2023;37(1):132-142

Agents: Liposomal clodronate; Liposome (control) Vehicle: Not Stated; Route: CSF/CNS; Species: Mice; Pump: 1004; Duration: 5 days;

ALZET Comments: Dose (0.11 μl/h,); Controls received mp w/ vehicle; animal info (23 week old male SAMP8/SAMR1 mice; Weighed 20-30 g); Brain Coordinates (2,8 mm anterior from posterior fontanelle, 1.2 mm lateral to sagitall suture); polyethylene catheter; dental cement used; aging;

（3）Ganciclovir

文献一：X. Zhang, et al. Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models. Stem Cell Reports 2021;16(1):89-105 Agents: Ganciclovir Vehicle: Saline; Route: SC; Species: Mice; Pump: 2004; Duration: 7 days;

ALZET Comments: Dose: (20 mg/kg/day); 0.9% sterile saline vehicle used; animal info: APP/PS1 (Jax, 34,832) and hAPP-J20 mice (Jax MMRRC, 034836); behavioral testing (MWM and Y-maze tests); Ganciclovir aka (GCV)neurodegenerative (Alzheimer's disease);

文献二：I. Jakovcevski, et al. Impact of Depletion of Microglia/Macrophages on Regeneration after Spinal Cord Injury. Neuroscience 2021;459(129-141

Agents: Ganciclovir Vehicle: PBS; Route: SC; Species: Mice; Pump: 1004; Duration: 28 days;

ALZET Comments: Dose (50 mg/ml); animal info (three-month-old female TK mice); spinal cord injury;

（4）Nucleic Acids

文献一：O. Gawrys, et al. Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats. Biochemical Genetics 2021;59(1):62-82

Agents: vascular endothelial growth factor, DNA Vehicle: Glucose; Route: CSF/CNS (medula); Species: Rat; Pump: 2001; Duration: 1 week;

ALZET Comments: 5% glucose used; Controls received mp w/ vehicle; animal info (Male, adult spontaneously hypertensive rats, 16 weeks old, 299 +- 4); Blood pressure measured via telemetry transmitters; vascular endothelial growth factor aka VEGF-A; ALZET brain infusion kit 2 used; gene therapy;

文献二：S. Wang, et al. Role of Extracellular MicroRNA-146a-5p in Host Innate Immunity and Bacterial Sepsis. iScience 2021;24(12):103441

Agents: microRNA-146a-5p Vehicle: Lipofectamine; Route: SC; Species: Mice; Pump: Not Stated; Duration: 3 days;

ALZET Comments: Dose (50 ug/mouse/day); animal info (Male; miR146a-KO; 9-12 weeks old; Weighed 20-30 g); immunology;

（5）Liposomes

文献一：S. Fujiwara, et al. Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury. In Vivo 2023;37(1):132-142

Agents: Liposomal clodronate: Liposome (control) Vehicle: Not Stated; Route: CSF/CNS; Species: Mice; Pump: 1004; Duration: 5 days;

ALZET Comments: Dose (0.11 μl/h,); Controls received mp w/ vehicle; animal info (23 week old male SAMP8/SAMR1 mice; Weighed 20-30 g); Brain Coordinates (2,8 mm anterior from posterior fontanelle, 1.2 mm lateral to sagitall suture); polyethylene catheter; dental cement used; aging;

（6）siRNA

文献一：D. Mao, et al. Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation. Bioengineered 2021;12(2):11823-11836

Agents: Brain derived neurotrophic factor, RNA, small interfering Vehicle: CSF, artificial; Route: CSF/CNS (right lateral ventricle); Species: Rat; Pump: Not Stated; Duration: Not Stated;

 ALZET Comments: animal info (Male Sprague Dawley; Weighed 200-250 g); behavioral testing (Rotarod test; Postural asymmetry; Head roll tilt; Nystagmus); tissue perfusion (Brain tissue); gene therapy;

文献二：D. S. Lee, et al. PDI-Mediated Reduction of Disulfide Bond on PSD95 Increases Spontaneous Seizure Activity by Regulating NR2A-PSD95 Interaction in Epileptic Rats Independent of S-Nitrosylation. International Journal of Molecular Sciences 2020;21(6):

Agents: RNA, small interfering (PDI) Vehicle: Not Stated; Route: CSF/CNS (right lateral ventricle); Species: Rat; Pump: 1007D; Duration: 7 days;

ALZET Comments: Animal info (Male Sprague Dawley rats, 7 weeks old); ALZET brain infusion kit 1 used; Brain coordinates (1 mm posterior; 1.5 mm lateral; 3.5 mm depth from bregma); neurodegenerative (Epilepsy);

（7）Morpholinos

文献一：M. Popek, et al. Physiology and Morphological Correlates of Excitatory Transmission are Preserved in Glutamine Transporter SN1-Depleted Mouse Frontal Cortex. Neuroscience 2020;446(124-136

Agents: Anti-SN1 vivo-morpholinos oligonucleotides Vehicle: Saline; Route: CNS/CSF; Species: Mice; Pump: 1002; Duration: Not stated;

ALZET Comments: Dose (1.2 mg/kg/day); Controls received mp w/ vehicle; animal info (Male, C57Bl6, 30 g); peptides; Brain coordinates (AP + 2.0, ML 0.8, DV 1.5)); neurodegenerative (Glutamatergic transmission);

文献二：M. McMillin, et al. FXR-Mediated Cortical Cholesterol Accumulation Contributes to the Pathogenesis of Type A Hepatic Encephalopathy. CMGH 2018;6(1):47-63

Agents: Farnesoid X receptor morpholino, FXR mismatch, Cyclodextrin 2-hydroxypropyl-beta Vehicle: Endo-Porter solution; Route: CSF/CNS; Species: Mice; Pump: Not Stated; Duration: Not Stated;

ALZET Comments: Dose (2-HbC, 6 mg/kg/day; FXR morpholino 1mg/kg; FXR mismatch 1 mg/kg); animal info (C57Bl/6 mice 25–30 g); ALZET brain infusion kit used; Brain coordinates (anteroposterior -0.34, mediolateral -1.0, and dorsoventricular -2.0);

（8）Viral Vectors

文献一：W. Q. Tang, et al. Virus-Mediated Decrease of LKB1 Activity in the mPFC Diminishes Stress-Induced Depressive-Like Behaviors in Mice. Biochemical Pharmacology 2022;197(114885

Agents: Virus, adeno-associated Vehicle: Not Stated; Route: Not Stated; Species: Mice; Pump: Not Stated; Duration: 14 days;

ALZET Comments: Dose (0.2 ul/min); animal info (8 weeks old; Male; Weighed 23-25 g; 50 weeks old CD1 mice male and female); behavioral testing (Forced swim test; Tail suspension test; Sucrose preference test; Social interaction test); bilateral cannula used; dental cement used; gene therapy; Therapeutic indication (Depression);

文献二：Z. Meszar, et al. CRISPR/Cas9-Based Mutagenesis of Histone H3.1 in Spinal Dynorphinergic Neurons Attenuates Thermal Sensitivity in Mice. International Journal of Molecular Sciences 2022;23(6):

Agents: Virus, adeno-associated, CRISPR Vehicle: Saline; Route: CSF/CNS (subarachnoid space); Species: Mice; Pump: 1003D; Duration: 3 days;

ALZET Comments: animal info (Male; 30 total; Between 24.9-34.1 g; 22 Pdyn::cas9-EGFP hybrids; 8 wild-type C57BL/6 mice); behavioral testing (Formalin test; Paw withdrawal latency); gene therapy; Therapeutic indication (Burn-injury-associated tissue damage);